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Results for second-order Møller-Plesset perturbation theory (MP2) do not alter the observed trend based on Density Functional Theory (DFT). The observed trends in reaction energy profile explain why the formation of D-2HG is preferred over l-2HG and reveal why mutation leads to the formation of d-2HG instead of l-2HG. For a better understanding of the observed difference in the activation barrier for the formation of the two alternative products, we performed natural bond orbital analysis, non-covalent interactions analysis and energy decomposition analysis. Our findings based on computational calculations clearly indicate a role for chiral discrimination in mutated enzymatic pathways in cancer biology.Multimorbid older men are increasingly more common in daily practice and present a challenge because they are often affected by lower urinary tract symptoms (LUTS) and age-associated benign prostatic hyperplasia (BPH). In order to identify possible risks in diagnostics, therapy and counselling at an early stage, screening for functional deficits or risk factors with standardized procedures is helpful. An initial screening with subsequent assessment of everyday skills using the Barthel Index, Timed up & Go Test, and a cognitive test are recommended. If frailty syndrome is detected, it should be taken into account during the pre-, peri-, and postoperative management, as it may indicate increased morbidity and mortality. Noninvasive methods for reducing the prostate volume without anesthesia can be a therapy option in older multimorbid patients, and with individual planning and consideration of risk factors, up to 70% of individuals become symptom-free. However, there is currently no gold standard for this vulnerable patient group. Number of medications and concomitant diseases and higher need for help are per se risk factors for unsatisfactory results after transurethral resection of the prostate (TURP) or laser vaporization. With drug therapy, concomitant medications and their interactions, especially in the cytochrome system, an existing multimorbidity and adherence to therapy must be taken into account. Combination therapies may complement each other and may bridge the time until surgery. Minimally invasive methods that can be performed without general anesthesia are suitable for geriatric patients, especially those with recurrent retention. Studies with the Rezüm® system (NxThera Inc., Maple Grove, MN, USA) and UroLift® (NeoTract Inc., Pleasanton, CA, USA) show that about 70% of patients can be relieved from the permanent catheter.

Some patients referred for transcatheter aortic valve replacement (TAVR) have excessively large annuli (ELA) without device options according to current sizing charts. This retrospective study aims to summarize the presentation and outcomes of ELA patients receiving first-generation self-expanding valves.

The TAVR database was reviewed in search for cases of self-expanding valves. Patients who had annuli exceeding the perimeter limit on the device sizing chart were referred to as the ELA group. Patients who had annuli within the range covered by the two largest sizes and received the corresponding valve size served as the control group (CG). Baseline, procedures, outcomes, and imaging characteristics on multislice computed tomography (MSCT), such as native anatomy and postimplant stent geometry, were compared.

Atotal of 28patients were included in the ELA group and 82in the CG. The patients in the ELA group were younger than those in the CG (72.5 ± 6.2 vs. 75.4 ± 5.8 years, P = 0.03). The median intended perimeter oversizing in relation to the annulus in the ELA group was much smaller than in the CG (-0.4 [-4.6, 4.1] % vs. 16.1 [11.7, 20.8] %, P < 0.01). The calcium burden in the aortic root was around 1.3-fold greater in the ELA group than the CG (756.0 [534.5, 1670.9] vs. 582.1 [310.3, 870.9] mm

, P = 0.01). The need for second valve implantation was higher in ELA (21.4% vs. 12.2%, P = 0.23) but no valve embolization was encountered. The 1‑year follow-up was comparable, including >mild paravalvular leak.

Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring.

Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring.Melanocortins are peptides that share a common central pharmacophor. Melanin pigmentation of interfollicular epidermis and hair via MC1R remains the key physiologic function of the naturally occurring melanocortin peptides in skin. Moreover, the melanocortins are crucially involved in the ultraviolet light-induced tanning response. Under pathophysiologic conditions, melanocortin peptides induce cutaneous hyperpigmentation, likewise via the MC1R axis, e.g. in patients with Addison’s disease, ectopic precursor pro-opiomelanocortin (POMC) syndrome and in those with abnormally elevated melanocortin blood levels. Translational research on α‑MSH (melanocyte-stimulating hormones) and their antagonists has further revealed a variety of other biological activities beyond pigmentation. PPAR agonist They include cytoprotection, antioxidative effects, regulation of collagen metabolism and fibrosis, sebum production, and cutaneous wound healing. These findings have also promoted the development of novel therapies in clinical dermatology including the exploitation of afamelanotide. In 2015, this agent became the first in-class synthetic α‑MSH analogue to be approved in dermatology for the treatment of erythropoetic protoporphyria. In addition to afamelanotide, setmelanotide has recently emerged as a highly selective MC4R agonist useful for the treatment of distinct forms of genetically determined obesity, e.g., POMC deficiency. Future perspectives in dermatology reside in treatment of other difficult-to-treat skin diseases with α‑MSH analogues, either with topical or systemic formulations. Moreover, synthetic melanocortin peptide derivatives lacking the central pharmacophor but with maintained anti-inflammatory effects could become a promising strategy for the design of new therapies in dermatology.