Guyvedel6724

Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent severe SCD pain is limited. This exploratory study sought to describe pain phenotypes based on frequency of severe pain experienced over 6 months and identify inflammatory biomarkers associated with pain phenotypes among individuals with SCD.

This study used self-report and electronic health record data collected from 74 individuals enrolled in the Duke Sickle Cell Disease Implementation Consortium Registry. Plasma from previously collected blood specimens was used to generate inflammatory biomarker data using the Inflammation 20-plex ProcartaPlex

panel. Descriptive statistics were used to describe the occurrence of severe pain over the past 6 months, and bi-variate analyses were used to evaluate the relationship between inflammatory biomarkers and pain phenotypes.

Among the 74 participants included in this study, 33.8% reported severe pain occurring never or rarely, 40.5% reported severe pain occurring sometimes, and 25.7% reported severe pain occurring often or always. Soluble E-selectin (sE-selectin) was the only inflammatory biomarker significantly associated with the pain phenotype groups (

= 0.049). Post hoc comparisons identified that participants in the often/always severe pain group had significantly higher plasma concentrations of sE-selectin compared to those in the sometimes severe pain group (

= 0.040).

Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.

Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.We evaluated the risk factors of deep venous thrombosis (DVT) after knee arthroscopic posterior cruciate ligament (PCL) reconstruction in patients with only PCL injury. From August 2014 to December 2020, a total of 172 patients who had accepted knee arthroscopic PCL reconstruction underwent the color Doppler ultrasound of bilateral lower-extremities deep veins on 3 days postoperatively. Based on the inspection results, patients were divided into DVT group (18 males and 8 females, mean age 43.62 years) and non-DVT group (108 males and 38 females, mean age 33.96 years). The potential associations of DVT risk and age, gender, body mass index (BMI), diabetes, hypertension, smoking and other factors were analyzed. An old age (OR = 1.090; 95% CI = 1.025-1.158; P = 0.006), a high BMI (OR = 1.509; 95% CI = 1.181-1.929; P = 0.001) and an increased post-surgery D-dimer (OR = 5.034; 95% CI = 2.091-12,117; P ≤ 0.001) value were significantly associated with an elevated DVT risk after knee arthroscopic PCL reconstruction. Increased age, BMI, and postoperative D-dimer were risk factors of DVT following knee arthroscopic PCL reconstruction in patients with only PCL injury.The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. In this study, we used animal models and human tissues to examine the role of vascular mTORC1 signaling in the endothelial dysfunction associated with obesity. In mice, obesity induced by high-fat/high-sucrose diet feeding for ∼2 mo resulted in aortic endothelial dysfunction without appreciable changes in vascular mTORC1 signaling. On the other hand, chronic high-fat diet feeding (45% or 60% kcal ∼9 mo) in mice resulted in endothelial dysfunction associated with elevated vascular mTORC1 signaling. Endothelial cells and visceral adipose vessels isolated from obese humans display a trend toward elevated mTORC1 signaling. Surprisingly, genetic disruption of endothelial mTORC1 signaling through constitutive or tamoxifen inducible deletion of endothelial Raptor (critical subunit of mTORC1) did not prevent or rescue the endothelial dysfunction associated with high-fat diet feeding in mice. Endothelial mTORC1 deficiency also failed to reverse the endothelial dysfunction evoked by a high-fat/high-sucrose diet in mice. Taken together, these data show increased vascular mTORC1 signaling in obesity, but this vascular mTORC1 activation appears not to be required for the development of endothelial impairment in obesity.Chronic intermittent hypoxia (CIH) is associated with diurnal hypertension, increased sympathetic nerve activity (SNA), and increases in circulating angiotensin II (ANG II). In rats, CIH increases angiotensin type 1 (AT1a) receptor expression in the median preoptic nucleus (MnPO), and pharmacological blockade or viral knockdown of this receptor prevents CIH dependent increases in diurnal blood pressure. The current study investigates the role of AT1a receptor in modulating the activity of MnPO neurons following 7 days of CIH. Male Sprague-Dawley rats received MnPO injections of an adeno-associated virus with a shRNA against the AT1a receptor or a scrambled control. Rats were then exposed to CIH 8 h a day for 7 days. JAK pathway In vitro loose patch recordings of spontaneous action potential activity were made from labeled MnPO neurons in response to brief focal application of ANG II or the GABAA receptor agonist muscimol. Additionally, MnPO KCC2 protein expression was assessed using Western blot. CIH impaired the duration but not the magnitude of ANG II mediated excitation in the MnPO. Both CIH and AT1a knockdown also impaired GABAA mediated inhibition and CIH with AT1a knockdown produced GABAA mediated excitation. Recordings using the ratiometric Cl- indicator ClopHensorN showed CIH was associated with Cl- efflux in MnPO neurons that was associated with decreased KCC2 phosphorylation. The combination of CIH and AT1a knockdown attenuated reduced KCC2 phosphorylation seen with CIH alone. The current study shows that CIH, through the activity of AT1a receptors, can impair GABAA mediated inhibition in the MnPO contributing sustained hypertension.