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1.
J Am Heart Assoc ; : e035269, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248265

RESUMEN

BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39218203

RESUMEN

OBJECTIVE: AMP-activated protein kinase (AMPK) dysregulation is implicated in osteoarthritis (OA), but the mechanisms underlying this dysregulation remain unclear. We investigated the role of cereblon, a substrate-recognition protein within the E3-ligase ubiquitin complex, in AMPK dysregulation and OA pathogenesis. METHODS: Cereblon expression was examined in human (n = 5) and mouse (n = 10) OA cartilage. The role of cereblon was investigated through its adenoviral overexpression (n = 10) or knockout (KO, n = 15) in the destabilization of the medial meniscus (DMM)-operated mice. The therapeutic potentials of the chemical cereblon degrader, TD-165, and the AMPK activator, metformin, were assessed through intra-articular (IA) injection to mice (n = 15). RESULTS: Immunostaining revealed that cereblon is upregulated in human and mouse OA cartilage. In DMM model mice, cartilage destruction was exacerbated by overexpression of cereblon in mouse joint tissues (OARSI grade; 1.11 [95% CI: 0.50 to 2.75]), but inhibited in global (-2.50 [95% CI: -3.00 to -1.17]) and chondrocyte-specific (-2.17 [95% CI: -3.14 to -1.06]) cereblon KO mice. The inhibitory effects were more pronounced in mice fed a high-fat diet compared to a regular diet. The degradation of cereblon through IA injection of TD-165 inhibited OA cartilage destruction (-2.47 [95% CI: -3.22 to -1.56]). Mechanistically, cereblon exerts its catabolic effects by negatively modulating AMPK activity within chondrocytes. Consistently, activation of AMPK by IA injection of metformin inhibited posttraumatic OA cartilage destruction (-1.20 ([95% CI: -1.89 to -0.45]). CONCLUSIONS: The cereblon-AMPK axis acts as a catabolic regulator of OA pathogenesis and seems to be a promising therapeutic target in animal models of OA.

4.
Br J Haematol ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39104032

RESUMEN

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

5.
J Clin Anesth ; 98: 111575, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39128258

RESUMEN

STUDY OBJECTIVE: Ultrasound-guided erector spinae plane block (ESPB) is commonly used for perioperative analgesia in adults; however, its analgesic efficacy and safety in pediatric patients remain uncertain. This review aimed to determine whether ultrasound-guided ESPB can improve analgesic efficacy and safety in pediatric surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Perioperative setting. PATIENTS: Pediatric patients undergoing elective surgery under general anesthesia. INTERVENTIONS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, KoreaMed, Web of Science, Scopus, and ClinicalTrials.gov databases for eligible published randomized controlled studies (RCTs) comparing ESPB with controls (no block or other block) in pediatric patients undergoing elective surgery under general anesthesia. MEASUREMENTS: The primary outcome was cumulative opioid consumption after surgery. Other outcomes included intraoperative opioid consumption, time to first request for rescue analgesia, number of patients requiring rescue analgesics, and pain scores after surgery. The safety outcomes were the incidences of bradycardia, hypotension, and postoperative vomiting. MAIN RESULTS: The analysis included 17 RCTs comprising 919 participants: 461 in the ESPB group, 269 in the no-block group (no block/sham block), and 189 in the other block group. Compared with the control group (no block and other blocks), ESPB significantly reduced the cumulative opioid consumption (intravenous morphine milligram equivalents) after surgery (standardized mean difference = -1.51; 95% confidence interval, -2.39 to -0.64; P = 0.0002; I2 = 92.9%) and intraoperative opioid consumption, and lowered average pain scores up to 24 h after surgery. ESPB extended the time to the first request for rescue analgesia and decreased the number of patients requiring rescue analgesics. Furthermore, ESPB lowered the pain score at most time points for 24 h after surgery, improved parental satisfaction, and reduced the incidence of postoperative vomiting compared with that in no block/sham block. CONCLUSIONS: ESPB provides effective and safe perioperative analgesia in pediatric patients undergoing elective surgery under general anesthesia.

6.
Aliment Pharmacol Ther ; 60(5): 563-584, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39086130

RESUMEN

BACKGROUND: Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis. AIMS: The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535). METHODS: In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health-related quality of life (HRQoL). We compared safety and efficacy between achievers and non-achievers of a multi-component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements. RESULTS: Data for completers (n = 250) and non-responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as-observed proportion of FIL200-treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non-responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid-free pMCS remission than non-achievers, up to LTE week 96. CONCLUSIONS: Filgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long-term benefit-risk profile. FIL200-treated CDC achievers had better long-term outcomes than non-achievers.


Asunto(s)
Colitis Ulcerosa , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Método Doble Ciego , Resultado del Tratamiento , Estudios de Seguimiento , Triazoles/uso terapéutico , Triazoles/efectos adversos , Triazoles/administración & dosificación , Piridinas/uso terapéutico , Piridinas/efectos adversos , Piridinas/administración & dosificación , Adulto Joven
7.
Transpl Int ; 37: 12574, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170864

RESUMEN

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.


Asunto(s)
Presión Sanguínea , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Aloinjertos , Anciano , Modelos de Riesgos Proporcionales , Rechazo de Injerto , Receptores de Trasplantes , Hipertensión
8.
Int J Food Microbiol ; 424: 110851, 2024 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-39116463

RESUMEN

The frozen fruit sector has experienced significant growth due to improved product quality as well as the advantage of long-term preservation. However, freezing alone does not eliminate foodborne viruses, a major public health concern and considerable economic burden. One promising disinfecting treatment is pulsed light, shown previously to inactivate hepatitis A virus (HAV) and murine norovirus-1 (MNV-1) on the surface of fresh berries. Viral loads were reduced by 1-2 log, with minor visual quality deterioration observed. In this study, an FDA-compliant pulsed light treatment (11.52 J/cm2) was applied to frozen fruits and berries. Infectious MNV-1 and HAV titers were reduced by 1-2 log on most frozen fruits. A noteworthy finding was that reductions of both viruses on cranberries exceeded 3.5 log cycles. Although pulsed light caused a measurable rise in temperature on the product surface, no visible physical changes (e.g., color) were observed, and the fruit pieces were still frozen after treatment. Although the reduction of infectious titer by pulsed light alone was not large (1-2 log), considering the low amount of virus typically found on fruit, it may be beneficial in the frozen fruit sector. It would be easy to combine with other treatments, and synergic interactions might increase virus inactivation.


Asunto(s)
Frutas , Virus de la Hepatitis A , Norovirus , Inactivación de Virus , Norovirus/efectos de la radiación , Virus de la Hepatitis A/efectos de la radiación , Virus de la Hepatitis A/fisiología , Virus de la Hepatitis A/crecimiento & desarrollo , Inactivación de Virus/efectos de la radiación , Animales , Luz , Ratones , Conservación de Alimentos/métodos , Microbiología de Alimentos , Congelación
9.
Sci Rep ; 14(1): 19587, 2024 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179667

RESUMEN

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.


Asunto(s)
Ado-Trastuzumab Emtansina , Sistemas de Registro de Reacción Adversa a Medicamentos , Neoplasias de la Mama , Farmacovigilancia , United States Food and Drug Administration , Humanos , Estados Unidos , Femenino , Ado-Trastuzumab Emtansina/efectos adversos , Ado-Trastuzumab Emtansina/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Bases de Datos Factuales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Trastuzumab/efectos adversos , Adulto , Antineoplásicos Inmunológicos/efectos adversos , Anciano , Enfermedades de las Vías Biliares/inducido químicamente , Hepatopatías/epidemiología
10.
BMC Med ; 22(1): 335, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148087

RESUMEN

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.


Asunto(s)
Clopidogrel , Citocromo P-450 CYP2C19 , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Inhibidores de la Bomba de Protones , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Masculino , Femenino , Stents Liberadores de Fármacos/efectos adversos , Anciano , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Resultado del Tratamiento , Sistema de Registros , Pueblos del Este de Asia
11.
Food Chem ; 461: 140808, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39151342

RESUMEN

This study compared the nutritional components, isoflavones, and antioxidant activities by solid-sate fermentation of Apios americana Medikus (AAM) with seven different fungi. The total fatty acid contents increased from 120.5 mg/100 g (unfermented AAM, UFAAM) to 242.0 to 3167.5 mg/100 g (fermented AAM, FAAM) with all fungi. In particular, the values of total fatty acids were highest (26.3-fold increase) in the FAAM with Monascus purpureus. The amount of total free amino acids increased from 591.69 mg/100 g (UFAAM) to 664.38 to 1603.07 mg/100 g after fermentation except for Monascus pilosus and Lentinula edodes. The total mineral contents increased evidently after fermentation with M. purpureus, F. velutipes, and Tricholoma matsutake (347.36 â†’ 588.29, 576.59, and 453.32 mg/100 g, respectively). The UFAAM predominated isoflavone glycosides, whereas glycoside forms were converted into aglycone forms after fermentation by fungi. The bioconversion rates of glycoside to aglycone were excellent in the FAAM with M. pilosus, M. purpureus, F. velutipes, and T. matsutake (0.01 â†’ 0.69, 0.50, 0.27, and 0.31 mg/g, respectively). Furthermore, the total phenolic contents, total flavonoid contents, and antioxidant activities by the abovementioned FAAM were high except for L.edodes. This FAAM can be used as a potential food and pharmaceutical materials.

12.
Nanoscale ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39157961

RESUMEN

Conventional DRAM, consisting of one transistor and one capacitor (1T1C), requires periodic data refresh processes due to its limited retention time and data-destructive read operation. Here, we propose and demonstrate a novel 3D-DRAM memory scheme available with a single transistor and a single ferroelectric field-effect transistor (FeFET) DRAM (2T0C-FeDRAM), which offers extended retention time and non-destructive read operation. This architecture uses a back-end-of-line (BEOL)-compatible amorphous oxide semiconductor (AOS) that is suitable for increasing DRAM cell density. Notably, the device structures of a double gate a-ITZO/a-IGZO FeFET, used for data storage and reading, are engineered to achieve an enlarged memory window (MW) of 1.5 V and a prolonged retention time of 104 s. This is accomplished by a double gate and an a-ITZO/a-IGZO heterostructure channel to enable efficient polarization control in hafnium-zirconium oxide (HZO) layers. We present successful program/erase operations of the double gate a-ITZO/a-IGZO FeFET through incremental step pulse programming (ISPP), demonstrating multi-level states with remarkable retention characteristics. Most importantly, we perform 2T0C-FeDRAM operations by electrically connecting the double gate a-ITZO/a-IGZO FeFET and the a-ITZO FET. Leveraging the impressive performance of the double gate a-ITZO/a-IGZO FeFET technology, we have effectively showcased an exceptionally record-long retention time exceeding 2000 s and 4-bit multi-level states, positioning it as a robust contender among emerging memory solutions in the era of artificial intelligence.

13.
Front Psychiatry ; 15: 1441102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119077

RESUMEN

Objective: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with developmental coordination disorder (DCD). This study aimed to evaluate the association between DCD symptoms and neuropsychological characteristics in children with and without ADHD. Methods: We recruited 298 children aged 5-12 years. Motor performance was assessed using the Developmental Coordination Disorder Questionnaire (DCDQ), while ADHD symptoms were assessed using the ADHD Rating Scale (ARS) and the Advanced Test of Attention (ATA). Cognitive characteristics were measured using the Wechsler Intelligence Scale, and behavioral characteristics were assessed using the Korean Personality Rating Scale for Children. Results: The children had a mean age of 7.6 ± 1.7 years, with 214 (71.8%) being boys. Among children diagnosed with ADHD (n = 176), 39.2% exceeded the DCDQ cutoff score, compared to 4.1% in the neurotypical group (n = 122). In the correlation analysis, the DCDQ total score was significantly correlated with ARS, omission and commission errors in visual and auditory ATA, and full-scale intellectual quotient. In addition, symptoms of depression, social dysfunction, and psychosis were correlated with the DCDQ total score. In the between-group analysis, children with both ADHD and DCD exhibited more omission errors on the auditory ATA and behavioral problems related to depression, social dysfunction, and psychosis compared to children with ADHD only. Conclusion: Our study indicates that children with ADHD exhibit more difficulties in motor performance. Children with both ADHD and DCD may present with a greater burden of psychiatric conditions than children with ADHD only, suggesting the need for careful monitoring in clinical practice.

14.
Gut Pathog ; 16(1): 44, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187879

RESUMEN

BACKGROUND: While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC). RESULTS: The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851). CONCLUSIONS: The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.

15.
Phytomedicine ; 133: 155926, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128302

RESUMEN

BACKGROUND: Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, is known for its effects on cancer and immunoregulation. HYPOTHESIS/PURPOSE: Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo, and in vitro models. STUDY DESIGN AND METHODS: We performed in silico-based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation. RESULTS: Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003. CONCLUSION: SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI.


Asunto(s)
Lesión Pulmonar Aguda , Angelica , Astragalus propinquus , Trampas Extracelulares , Inflamasomas , Lipopolisacáridos , Ratones Endogámicos C57BL , Neutrófilos , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Trampas Extracelulares/efectos de los fármacos , Ratones , Neutrófilos/efectos de los fármacos , Humanos , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Astragalus propinquus/química , Masculino , Angelica/química , Medicamentos Herbarios Chinos/farmacología , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad
16.
Ultrasonography ; 43(5): 299-313, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39086070

RESUMEN

Medial elbow pain is a common musculoskeletal problem among individuals engaging in repetitive activities. Medial epicondylitis is the predominant cause of this pain. However, other potential causes must be considered as part of the differential diagnosis. This article discusses several etiologies of medial elbow pain, including medial epicondylitis, ulnar neuropathy, snapping triceps syndrome, ulnar collateral ligament injury, medial antebrachial cutaneous neuropathy, and diseases of the elbow joint, with an emphasis on ultrasound (US) findings. Awareness of possible diagnoses and their US features can assist radiologists in establishing a comprehensive diagnosis for medial elbow pain.

17.
Animals (Basel) ; 14(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39199847

RESUMEN

Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1-4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators.

18.
Diagnostics (Basel) ; 14(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39202189

RESUMEN

Brain swelling after cardiac arrest may affect brain ventricular volume. This study aimed to investigate the prognostic implications of ventricular volume on early thin-slice brain computed tomography (CT) after cardiac arrest. We measured the gray-to-white matter ratio (GWR) and the characteristics and volumes of the lateral, third, and fourth ventricles. The primary outcome was a poor 6-month neurological outcome. Of the 166 patients, 115 had a poor outcome. The fourth ventricle was significantly smaller in the poor outcome group (0.58 cm3 [95% CI, 0.43-0.80]) than in the good outcome group (0.74 cm3 [95% CI, 0.68-0.99], p < 0.001). Ventricular characteristics and other ventricular volumes did not differ between outcome groups. The area under the curve for the fourth ventricular volume was 0.68, comparable to 0.69 for GWR. Lower GWR (<1.09) and lower fourth ventricular volume (<0.41 cm3) predicted poor outcomes with 100% specificity and sensitivities of 8.7% (95% CI, 4.2-15.4) and 20.9% (95% CI, 13.9-29.4), respectively. Combining these measures improved the sensitivity to 25.2% (95% CI, 17.6-34.2). After adjusting for covariates, the fourth ventricular volume was independently associated with neurologic outcome. A marked decrease in fourth ventricular volume, with concomitant hypoattenuation on CT scans, more accurately predicted outcomes.

19.
Women Health ; 64(8): 674-686, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39192526

RESUMEN

Functional gastrointestinal disorders (FGIDs) are common in young adults, particularly women, who tend to develop multiple FGIDs over time. This study aimed to investigate the prevalence of multiple concurrent FGIDs among female university students and identify differences in dietary habits, academic stress, and quality of life (QOL) based on the number of concurrent FGIDs. This secondary analysis included data from 406 female participants, originally collected through an online survey from two universities in one city in Korea. The online survey was accessible only after participants were verified as students through their online community. Concurrent FGID was present in 25.8 percent (n = 16) of the participants with FGIDs (n = 62), with the most common being irritable bowel syndrome + functional dyspepsia overlap (43.8 percent, 7/16). Participants with multiple concurrent FGIDs consumed fewer grains and vegetables, while significantly more of them consumed instant food, fast food, milk, and tea/coffee. They experienced significantly higher academic stress and lower QOL than those without the disease. Female university students with concurrent FGIDs tend to have unhealthy dietary habits, and concurrent FGIDs negatively affect academic stress and QOL. Therefore, female university students should undergo early-stage screening for FGIDs, and a comprehensive program should address their dietary habits and stress-coping skills.


Asunto(s)
Conducta Alimentaria , Enfermedades Gastrointestinales , Calidad de Vida , Estrés Psicológico , Estudiantes , Humanos , Femenino , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , República de Corea/epidemiología , Universidades , Enfermedades Gastrointestinales/epidemiología , Adulto Joven , Prevalencia , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Adulto , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/psicología , Estudios Transversales , Dispepsia/epidemiología , Adolescente
20.
Clin Exp Nephrol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39168881

RESUMEN

BACKGROUND: This study aimed to evaluate the association between phase angle, muscle strength, and muscle mass in patients undergoing kidney transplantation. METHODS: Patients whose pre- and follow-up phase angles were measured after kidney transplantation were enrolled. Phase angle and body composition were measured using a multi-frequency bioimpedance analysis device before and at 7 and 14 days and 3, 6, and 12 months after transplantation. Muscle strength was evaluated using handgrip strength (HGS). Low HGS was defined as < 28 kg in males and < 18 kg in females. Low muscle mass was defined as an appendicular lean mass index of < 7.0 kg/m2 in males and < 5.7 kg/m2 in females. RESULTS: Eighty-eight patients (mean age 52.3 ± 10.1 years) were analyzed. The mean phase angle of pre-transplantation was 5.0 ± 1.0°. Body fat percentage was significantly higher at 6 and 12 months after transplantation than pre-transplantation (P < 0.0001). Twelve months after kidney transplantation, the prevalence of low HGS decreased (pre-transplantation vs. 12 months post-transplantation: 28.4% vs. 17.0%), and the prevalence of low muscle mass (pre-transplantation vs. 12 months post-transplantation: 21.6% vs. 28.4%) increased. The pre-transplantation phase angle was significantly associated with low muscle mass at 12 months after kidney transplantation (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.16-0.72; P = 0.005). The pre-transplantation phase angle was not significantly associated with low HGS (OR: 0.37; 95% CI 0.12-1.17; P = 0.090) 12 months after kidney transplantation. CONCLUSIONS: Pre-transplantation phase angle can predict muscle mass status 12 months after kidney transplantation.

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