Seerupdugan5127
Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro-resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A4 (LXA4 ) and lipoxin B4 (LXB4 ), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high-affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB4 enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. BMS493 This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB4 displayed more potent effects than LXA4 in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual.Litter size is one of the important economic traits of livestock. Seasonal oestrus, ovulation and lambing of sheep have severely restricted the development of sheep farming in Xinjiang, China. The purpose of this study was to investigate the polymorphisms and genetic correlation between GRM1, GNAQ and HCRTR1 genes and the seasonal reproduction and litter size in three sheep breeds. The DNA mixed pool sequencing and PCR-SSCP methods were used to detect single nucleotide polymorphisms (SNPs) of GRM1, GNAQ and HCRTR1 genes in seasonal oestrous (Kazakh and Chinese Merino [Xinjiang Junken type]) and perennial oestrous (Hu) sheep breeds. The association between genetic polymorphism and litter size was also analysed. The results showed that T945C in exon 2 of GRM1 gene, C589T in exon 2 of HCRTR1 gene and A191G in exon 2 of GNAQ gene were identified by Sanger sequencing, and three genotypes were existed in each SNP site, which all belonged to the synonymous mutation. GRM1 (CC), GNAQ (GA) and HCRTR1 (TC) were the dominant genotypes of seasonal reproduction and litter size in Kazakh sheep and Chinese Merino sheep, respectively, while, in perennial oestrous Hu sheep populations, the dominant genotypes were GRM1 (TC), GNAQ (GA) and HCRTR1 (TC), respectively, and association analysis also confirmed the results. The above results implied that GRM1, GNAQ and HCRTR1 genes are significantly associated with lambing traits in Kazakh, Chinese Merino and Hu sheep. Among them, the locus of GRM1 (T945C), GNAQ (A191G) and HCRTR1 (C589T) might be considered as a potential molecular marker, which controls seasonal reproduction and litter size in sheep.
Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid-related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients.
Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full-text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included.
A total of 16 observational studies were included, with only two stuss of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors.
The current lack of agreement regarding standardized terminology in musculoskeletal and sports ultrasound presents challenges in education, clinical practice, and research. This consensus was developed to provide a reference to improve clarity and consistency in communication.
A multidisciplinary expert panel was convened consisting of 18 members representing multiple specialty societies identified as key stakeholders in musculoskeletal and sports ultrasound. A Delphi process was used to reach consensus which was defined as group level agreement >80%.
Content was organized into seven general topics including 1) General Definitions, 2) Equipment and Transducer Manipulation, 3) Anatomic and Descriptive Terminology, 4) Pathology, 5) Procedural Terminology, 6) Image Labeling, and 7) Documentation. Terms and definitions which reached consensus agreement are presented herein.
The historic use of multiple similar terms in the absence of precise definitions has led to confusion when conveying information between colleagues, patients, and third-party payers. This multidisciplinary expert consensus addresses multiple areas of variability in diagnostic ultrasound imaging and ultrasound-guided procedures related to musculoskeletal and sports medicine.
The historic use of multiple similar terms in the absence of precise definitions has led to confusion when conveying information between colleagues, patients, and third-party payers. This multidisciplinary expert consensus addresses multiple areas of variability in diagnostic ultrasound imaging and ultrasound-guided procedures related to musculoskeletal and sports medicine.
Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are the most common gnathic fibro-osseous lesions. These diseases exhibit remarkable overlap of several clinicopathological aspects, and differential diagnosis depends on the combination of histopathological, radiographic, and clinical aspects. Their molecular landscape remains poorly characterized, and herein, we assessed their proteomic and phosphoproteomic profiles.
The quantitative differences in protein profile of FD and COF were assessed by proteomic and phosphoproteomic analyses of formalin-fixed paraffin-embedded tissue samples. Pathway enrichment analyses with differentially regulated proteins were performed.
FD and COF exhibited differential regulation of pathways related to extracellular matrix organization, cell adhesion, and platelet and erythrocytes activities. Additionally, these lesions demonstrated distinct abundance of proteins involved in osteoblastic differentiation and tumorigenesis and differential abundance of phosphorylation of Ser61 of Yes-associated protein 1 (YAP1).
In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro-osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation.
In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro-osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation.
The aim of this investigation was to explore and characterize alterations in coronary circulatory function in function of increasing body weight with medically controlled cardiovascular risk factors and, thus, "metabolically" unhealthy obesity.
We prospectively enrolled 106 patients with suspected CAD but with normal stress-rest myocardial perfusion on
N-ammonia PET/CT and with medically controlled or no cardiovascular risk factors.
N-ammonia PET/CT concurrently determined myocardial blood flow (MBF) during pharmacologically induced hyperaemia and at rest. Based on body mass index (BMI), patients were grouped into normal weight (BMI 20.0-24.9kg/m
, n=22), overweight (BMI 25.0-29.9kg/m
, n=27), obese (BMI 30.0-39.9kg/m
, n=31), and morbidly obese (BMI≥40kg/m
, n=26).
Resting MBF was comparable among groups (1.09±0.18 vs. 1.00±0.15 vs. 0.96±0.18 vs.. 1.06±0.31ml/g/min; p=.279 by ANOVA). Compared to normal weight individuals, the hyperaemic MBF progressively decreased in in overweight and obese groups, respectively (2.54±0.48 vs. 2.02±0.27 and 1.75±0.39ml/g/min; p<.0001), while it increased again in the group of morbidly obese individuals comparable to normal weight (2.44±0.41 vs. 2.54±0.48ml/g/min, p=.192). The BMI of the study population correlated with the hyperaemic MBF in a quadratic or U-turn fashion (r=.34, SEE=0.46; p≤.002).
The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.
The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.
To examine the combined effects of cardiorespiratory fitness (CRF) and prediabetes or diabetes on cardiovascular and noncardiovascular mortality.
This prospective study evaluated a population-based cohort of 1562men aged 42-60years at baseline (1984-1989). We utilized maximal oxygen uptake (VO
) for assessing aerobic capacity and CRF in the cohort and stratified participants into six groups according to both their glucose status (diabetes, prediabetes, or no diabetes) and whether they were below- or above-median VO
. Deaths in the cohort were recorded till December 31 2016. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for cardiovascular and noncardiovascular mortality. Smoking, alcohol consumption, BMI, blood pressure, cholesterol, diagnosis of ischemic heart disease, and socioeconomic status served as covariates in the mortality analyses.
During the follow-up (mean 24.2years), 341men died from cardiovascular and 468men from noncardiovascular causes. When compared to men with no diabetes and above-median VO
, the presence of either diabetes (HR=4.10, 95% CI 2.27-7.40) or prediabetes (HR=2.10, 95% CI 1.18-3.73) combined with below-median VO
increased the risk of cardiovascular death. Noncardiovascular mortality was increased by low oxygen uptake in men with prediabetes (HR=2.24, 95% CI 1.30-3.84), and among men with diabetes, the increase was not statistically significant (HR=1.99, 95% CI 0.91-4.32).
Cardiorespiratory fitness modifies the risk of death related to prediabetes and diabetes. This highlights the importance of CRF assessment and interventions to support the uptake of regular physical activity among aging men with disturbed glucose metabolism.
Cardiorespiratory fitness modifies the risk of death related to prediabetes and diabetes. This highlights the importance of CRF assessment and interventions to support the uptake of regular physical activity among aging men with disturbed glucose metabolism.
