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Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction
No full textDiltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse. Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients. We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF). The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ± 6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses. In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality
D" Reflection Polarities Inform Lowermost Mantle Mineralogy
No full textPolarities of seismic reflections at the discontinuity atop the D" region (PdP and SdS) indicate the sign of the velocity contrast across the D" reflector. Recent studies found PdP polarities matching and opposite those of 'P' and PcP. While anisotropy could explain this behavior, we find that the ratio of the change in 'S' wave velocity over change in 'P' wave velocity (R-value) can influence polarity behavior of D" reflected 'P' waves. For 'R-values' exceeding 3, the 'P' wave reverses polarity in the absence of anisotropy while 'S' wave polarity is not influenced by the 'R-value'. Using sets of one million models for normal mantle and MORB with varying minerals and processes across the boundary, we carry out a statistical analysis (Linear Discriminant Analysis) finding that there is a marked difference in mantle mineralogy to explain R-values larger and smaller than 3, respectively. Based on our results we can attribute different mineralogy to a number of cases. In particular, we find that when velocities increase across D" and polarities of PdP and SdS are opposite the post-perovskite phase transition is still the best explanation whereas MORB is the best explanation when PdP and SdS are the same. When the velocities are decreasing, the post-perovskite phase transition within MORB is the best explanation if PdP and SdS polarities are the same but if PdP and SdS are opposite, our results indicate that primordial material or mantle enriched in bridgmanite can explain the polarity behavior, further constraining mineralogy within the large low seismic velocity provinces
Dynamic Parameters of Hypothermic Machine Perfusion—An Image of Initial Graft Function in Adult Kidney Transplantation?
No full textKidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5–28.5] vs. 11.3 [5.4–24.1], p < 0.0001). The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts (arterial flow 22.50 [18.00–48.00] vs. 51.83 [25.50–92.67] ml/min, p = 0.0256; organ resistance 123.33 [57.67–165.50] vs. 51.33 [28.17–111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08–7.64] vs. 1.67 [0.90–6.56], p < 0.0001) and at 1 year post transplant (1.80 [1.09–7.95] vs. 1.59 [0.87–7.40], p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome
Equivalence of Fell bundles is an equivalence relation
No full textWe introduce the notion of groupoid pre-equivalences and prove that they give
rise to groupoid equivalences by taking certain quotients. Then, given an equivalence of Fell bundles B and C and another equivalence between C and D over locally compact Hausdorff étale groupoids, we construct an equivalence between B and D out of the tensor product bundle. As a consequence, we obtain that Fell bundle equivalence is indeed an equivalence relation
Measurement of Postoperative Quality of Pain in Abdominoplasty Patients—An Outcome Oriented Prospective Study
No full text(1) Background: Postoperative pain is a frequently underestimated complication significantly influencing surgical outcome and patient satisfaction. While abdominoplasty is one of the most commonly performed plastic surgery procedures, studies investigating postoperative pain are limited in current literature. (2) Methods: In this prospective study, 55 subjects who underwent horizontal abdominoplasty were included. Pain assessment was performed by using the standardized questionnaire of the Benchmark Quality Assurance in Postoperative Pain Management (QUIPS). Surgical, process and outcome parameters were then used for subgroup analysis. (3) Results: We found a significantly decreased minimal pain level in patients with high resection weight compared to the low resection weight group (p = 0.01 *). Additionally, Spearman correlation shows significant negative correlation between resection weight and the parameter “Minimal pain since surgery” (rs = −0.332; p = 0.013). Furthermore, average mood is impaired in the low weight resection group, indicating a statistical tendency (p = 0.06 and a Χ2 = 3.56). We found statistically significant higher maximum reported pain scores (rs = 0.271; p = 0.045) in elderly patients. Patients with shorter surgery showed a statistically significant (Χ2 = 4.61, p = 0.03) increased claim for painkillers. Moreover, “mood impairment after surgery” shows a dramatic trend to be enhanced in the group with shorter OP duration (Χ2 = 3.56, p = 0.06). (4) Conclusions: While QUIPS has proven to be a useful tool for the evaluation of postoperative pain therapy after abdominoplasty, only continuous re-evaluation of pain therapy is a prerequisite for constant improvement of postoperative pain management and may be the first approach to develop a procedure-specific pain guideline for abdominoplasty. Despite a high satisfaction score, we detected a subpopulation with inadequate pain management in elderly patients, patients with low resection weight and a short duration of surgery
Oscillatory Correlates of Intentional Forgetting: The Role of Theta and Alpha Power in Item-Method Directed Forgetting
No full textResults from item-method directed forgetting suggest that individuals are able to intentionally forget processed information. Most research suggests that either selective rehearsal of to-be-remembered or inhibitory control of to-be-forgotten information is accountable for the effects of intentional forgetting. Some research, however, hypothesized that the time to process information mediates the underlying mechanism. To test this hypothesis, the current study investigated associations between oscillatory power in theta (3–7.5 Hz) and alpha frequencies (8–13 Hz) and intentional forgetting in human participants and explored whether or not these mechanisms depended on processing time. Previously, theta power was shown to be associated with the creation of episodic memory traces and alpha power with inhibition. We therefore expected to find associations between these neural signatures and behavioral effects. Consistent with our hypotheses, we revealed increased theta power for to-be-remembered and increased alpha power for to-be-forgotten information and that the effects of activity in both frequency bands were influenced by the time individuals were given for processing the memory cue. These results suggest that not one but two mechanisms, rehearsal and inhibitory control, are accountable for item-method directed forgetting, both with different temporal profiles
Pharmacological Potential of 3-Benzazepines in NMDAR-Linked Pathophysiological Processes
No full textThe number of 'N-Methyl-D-aspartate' receptor (NMDAR) linked neurodegenerative diseases such as Alzheimer's disease and dementia is constantly increasing. This is partly due to demographic change and presents new challenges to societies. To date, there are no effective treatment options. Current medications are nonselective and can lead to unwanted side effects in patients. A promising therapeutic approach is the targeted inhibition of NMDARs in the brain. NMDARs containing different subunits and splice variants display different physiological properties and play a crucial role in learning and memory, as well as in inflammatory or injury processes. They become overactivated during the course of the disease, leading to nerve cell death. Until now, there has been a lack of understanding of the general functions of the receptor and the mechanism of inhibition, which need to be understood in order to develop inhibitors. Ideal compounds should be highly targeted and even splice-variant-selective. However, a potent and splice-variant-selective NMDAR-targeting drug has yet to be developed. Recently developed 3-benzazepines are promising inhibitors for further drug development. The NMDAR splice variants GluN1-1b-4b carry a 21-amino-acid-long, flexible exon 5. Exon 5 lowers the NMDAR's sensitivity to allosteric modulators by probably acting as an NMDAR modulator itself. The role of exon 5 in NMDAR modulation is still poorly understood. In this review, we summarize the structure and pharmacological relevance of tetrahydro-3-benzazepines
