Clinical Oral Investigations - The aim of this study was to assess the correlation between chronic stress and temporalis muscle activity during four nights. Forty-four female subjects were... 相似文献
The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization. 相似文献
International Journal of Legal Medicine - In cases of crimes involving blood, the perpetrators often attempt to remove the traces they have left behind. Setting fire to the crime scene, aside from... 相似文献
We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.
Methods
The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.
Results
At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05–7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04–10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24–9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01–0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08–2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28–2.84, P < 0.01].
Conclusion
At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.
Journal of Neurology - Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene–environment interactions have been found... 相似文献
Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system.
Methods
To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging.
Results
Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group.
Conclusion
Our findings extend prior work by pointing to a biological signature of the “allostatic costs” of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.
The technique of pedicle screw stabilization is finding increasing popularity for use in the cervical spine. Implementing anterior transpedicular screws (ATPS) in cervical spine offers theoretical advantages compared to posterior stabilization. The goal of the current study was the development of a new setting for navigated insertion of ATPS, combining the advantage of reduced invasiveness of an anterior approach with the technical advantages of navigation.
Methods
20 screws were implanted in levels C3 to C6 of four cervical spine models (SAWBONES® Cervical Vertebrae with Anterior Ligament) with the use of 3D fluoroscopy navigation system [Arcadis Orbic 3D, Siemens and VectorVision fluoro 3D trauma software (BrainLAB)]. The accuracy of inserted screws was analyzed according to postoperative CT scans and following the modified Gertzbein and Robbins classification.
Results
20 anterior pedicle screws were placed in four human cervical spine models. Of these, eight screws were placed in C3, two screws in C4, six screws in C5, and four screws in C6. 16 of 20 screws (80 %) reached a grade 1 level of accuracy according to the modified Gertzbein and Robbins Classification. Three screws (15 %) were grade 2, and one screw (5 %) was grade 3. Grade 4 and 5 positions were not evident. Summing grades 1 and 2 together as “good” positions, 95 % of the screws achieved this level. Only a single screw did not fulfill these criteria.
Conclusion
The setting introduced in this study for navigated insertion of ATPS into cervical spine bone models is well implemented and shows excellent results, with an accuracy of 95 % (Gertzbein and Robbins grade 2 or better). Thus, this preliminary study represents a prelude to larger studies with larger case numbers on human specimens.
