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Background: The long-term goal of anterior cruciate ligament (ACL) reconstruction is to prevent secondary osteoarthritis due to instability. Obesity itself is also a risk factor for osteoarthritis and shows an increase in its incidence, but little is known about the relationship between obesity and the outcome of ACL reconstruction. Purpose/Hypothesis: This study aimed to determine the relationship between the outcome of ACL reconstruction and obesity. It was hypothesized that obesity would be associated with the revision rate of ACL reconstruction and additional surgical treatment for osteoarthritis in patients who undergo ACL reconstruction. Study design: Cohort study; Level of evidence, 3. Methods: Claims and health screening data of the National Health Insurance Service were used to analyze patients who underwent ACL reconstruction between January 1, 2003, and December 31, 2021. The association between obesity and risk of revision ACL reconstruction and additional surgical treatment for osteoarthritis or meniscal lesion was analyzed. Body mass index (BMI) was used to classify patients as underweight (BMI, <18.5), normal weight (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), obese (BMI, 30.0-39.9), or morbidly obese (BMI, ≥40.0). Multivariable Cox proportional hazards model analysis was conducted. Results: A total of 56,734 patients were included. Of them, 311 (0.5%) patients were underweight, 26,613 (46.9%) were normal weight, 24,372 (43.0%) were overweight, 5324 (9.4%) were obese, and 114 (0.2%) patients were morbidly obese. The underweight group showed a significantly lower risk of revision ACL reconstruction than the normal weight group (hazard ratio [HR], 0.54; 95% CI, 0.31-0.93; P = .0273). However, the overweight, obese, and morbidly obese groups had no significant difference from the normal weight group. The risk of high tibial osteotomy (HTO) or total knee arthroplasty (TKA) was significantly high for the overweight (HR, 1.93; 95% CI, 1.70-2.19; P < .0001) and obese (HR, 2.71; 95% CI, 2.23-3.30; P < .0001) groups. Subgroup analysis performed in patients ≥40 years of age for the risk of HTO showed a significant increased risk in the overweight group (HR, 1.889; 95% CI, 1.56-2.29; P < .0001) and obese group (HR, 2.78; 95% CI, 2.10-3.69; P < .0001). Subgroup analysis performed in patients ≥50 years of age for the risk of TKA also showed a significant increased risk in the overweight group (HR, 2.03; 95% CI, 1.67-2.47; P < .0001) and obese group (HR, 2.53; 95% CI, 1.83-3.50; P < .0001). After adjusting for meniscal injury at index surgery by multivariate regression analysis, 1.87- and 2.75-fold increased risks of HTO were identified for the overweight and obese groups, respectively, for patients aged >40 years. For patients aged >50 years, 2.02-fold and 2.52-fold increased risks of TKA were observed for the overweight and obese groups, respectively. The risk of additional surgery due to the meniscal lesion was high for the overweight (HR, 1.09; 95% CI, 1.03-1.15; P = .002) and obese (HR, 1.10; 95% CI, 1.01-1.21; P = .0351) groups, while no significant difference was found for the underweight and morbidly obese groups. Conclusion: This study highlights that obesity does not increase the revision rate of ACL reconstruction. However, the risk of additional surgical treatment for osteoarthritis and meniscal lesions increased as BMI increased. Further investigation is needed to determine the efficacy of ACL reconstruction for preventing osteoarthritis in obese patients.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta plaques and hyperphosphorylated tau proteins, leading to cognitive decline and neuronal death. However, despite extensive research, there are still no effective treatments for this condition. In this study, a series of chloride-substituted Ramalin derivatives is synthesized to optimize their antioxidant, anti-inflammatory, and their potential to target key pathological features of Alzheimer's disease. The effect of the chloride position on these properties is investigated, specifically examining the potential of these derivatives to inhibit tau aggregation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity. Our findings demonstrate that several derivatives, particularly RA-3Cl, RA-4Cl, RA-26Cl, RA-34Cl, and RA-35Cl, significantly inhibit tau aggregation with inhibition rates of approximately 50%. For BACE-1 inhibition, Ramalin and RA-4Cl also significantly decrease BACE-1 expression in N2a cells by 40% and 38%, respectively, while RA-23Cl and RA-24Cl showed inhibition rates of 30% and 35% in SH-SY5Y cells. These results suggest that chloride-substituted Ramalin derivatives possess promising multifunctional properties for AD treatment, warranting further investigation and optimization for clinical applications.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Proteínas tau , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Humanos , Proteínas tau/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/metabolismo , Cloruros/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Agregado de Proteínas/efectos de los fármacos , Línea Celular Tumoral , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/químicaRESUMEN
Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4ß-hydroxy-8ß-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.
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FN-kappa B , Nardostachys , Fenoles , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Nardostachys/metabolismo , Interferón gamma/metabolismo , Queratinocitos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismoRESUMEN
INTRODUCTION: Early diagnosis and aggressive treatment of pulmonary embolism (PE) are crucial for preventing severe complications after total knee arthroplasty (TKA). This study aimed to examine the efficacy of measuring oxygen saturation (SpO2) using a pulse oximeter for early diagnosis of PE after total knee arthroplasty (TKA). MATERIALS AND METHODS: We consecutively examined 1645 patients who underwent TKA between January 2015 and November 2019. Postoperative SpO2 was measured with a pulse oximeter, which was stopped if SpO2 was maintained at ≥ 95% until postoperative day 2 (POD2). To diagnose PE, computed tomographic pulmonary angiography (CTPA) was performed for specific indications, including persistently low SpO2 < 95% (group 1), sudden decrease in SpO2 (group 2), and decrease in SpO2 after POD3 with presenting symptoms (group 3). Also, we divided the patients into unilateral, simultaneous and sequential TKA groups and compared the results with specific statistical techniques. RESULTS: Of the 1645 patients who underwent TKA, there were 20 patients with PE (1.2%), and symptomatic PE was observed in only 4 patients (0.24%). CTPA was performed in 58 (3.5%) patients, of whom 20 were diagnosed with PE. In groups 1 (n = 34), 2 (n = 21), and 3 (n = 3), CTPA was performed 2.4, 2.6, and 8.3 days after TKA, respectively, and 12, 8, and 0 patients were diagnosed with PE, respectively. Of the 782, 416, and 447 unilateral, simultaneous, and sequential (done in same admission with interval 1 or 2 weeks) patients with TKA, 38, 18, and 2 received CTPA, and 13, 6, and 1 were diagnosed with PE, respectively. All patients diagnosed with PE have persistently low SpO2 < 95% (group 1), or sudden decrease in SpO2 (group 2) until POD2. Of the patients diagnosed with PE, SpO2 decreased without the presentation of symptoms in 16 patients (11 and 5 from groups 1 and 2, respectively) and with the presentation of symptoms, such as mild dyspnea and chest discomfort, in 4 patients (1 and 3 from groups 1 and 2, respectively). CONCLUSIONS: Measuring SpO2 using a pulse oximeter until POD2 was an effective method for early diagnosis of PE after TKA. No case of morbidity or mortality was observed after early diagnosis with early stage CTPA and management of PE. We recommend measuring SpO2 with a pulse oximeter for early diagnosing of PE in TKA.