RepoMed (Medizinische Hochschule Hannover)
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Lipase-Catalyzed Chemoselective Ester Hydrolysis of Biomimetically Coupled Aryls for the Synthesis of Unsymmetric Biphenyl Esters.
No full textLipases are among the most frequently used biocatalysts in organic synthesis, allowing numerous environmentally friendly and inexpensive chemical transformations. Here, we present a biomimetic strategy based on iron(III)-catalyzed oxidative coupling and selective ester monohydrolysis using lipases for the synthesis of unsymmetric biphenyl-based esters under mild conditions. The diverse class of biphenyl esters is of pharmaceutical and technical relevance. We explored the potency of a series of nine different lipases of bacterial, fungal, and mammalian origin on their catalytic activities to cleave biphenyl esters, and optimized the reaction conditions, in terms of reaction time, temperature, pH, organic solvent, and water-organic solvent ratios, to improve the chemoselectivity, and hence control the ratio of unsymmetric versus symmetric products. Elevated temperature and increased DMSO content led to an almost exclusive monohydrolysis by the four lipases Candida rugosa lipase (CRL), Mucor miehei lipase (MML), Rhizopus niveus lipase (RNL), and Pseudomonas fluorescens lipase (PFL). The study was complemented by in silico binding predictions to rationalize the observed differences in efficacies of the lipases to convert biphenyl esters. The optimized reaction conditions were transferred to the preparative scale with high yields, underlining the potential of the presented biomimetic approach as an alternative strategy to the commonly used transition metal-based strategies for the synthesis of diverse biphenyl esters
Reiber's Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis?
No full textOligoclonal bands are the gold standard for determination of an intrathecal immunoglobulin G synthesis and were recently included in the McDonald criteria of 2017 to diagnose relapsing multiple sclerosis (MS) as a substitute for dissemination in time. Intrathecally produced kappa free light chains (KFLC) are a novel promising biomarker with similar characteristics and the advantage for automated determination. However, different approaches exist to determine the intrathecal KFLC fraction. The most common method is to calculate the CSF/serum KFLC quotient with reference to the albumin CSF/serum quotient (QKappa/QAlb) the so-called KFLC index. Recently, Reiber developed a theoretically and empirically founded hyperbolic function similar to his traditional hyperbolic function for the immunoglobulins A, G, M. Our study included a total of 168 patients with either MS according to the McDonald criteria of 2017, clinically isolated syndrome (CIS) with conversion to MS during follow-up, or stable CIS. Positive oligoclonal bands were compared with the KFLC index, Reiber's KFLC diagram, Presslauer's KFLC exponential curve, and Senel's linear curve for KFLC. Reiber's diagram detected an intrathecal production of KFLC in 98/100 patients with MS, only one patient fewer than oligoclonal bands positivity (99/100). By using the KFLC index ≥ 5.9, Presslauer's KFLC exponential function, and Senel's linear curve two more patients would not have been identified (96/100). For the group of patients who converted from CIS to MS similar results were obtained for both the oligoclonal bands and the Reiber graph (21/24, 88%). The KFLC index ≥ 5.9, Presslauer's method, and Senel's linear function each identified two patients fewer (19/24, 79%). In patients with stable CIS, 11/44 patients (25%) displayed oligoclonal bands in contrast to 9/44 patients (20%) with elevated KFLC by using Reiber's diagram and Presslauer's method, 8/44 patients (18%) with elevated KFLC as detected by Senel's linear function, and 7/44 patients (16%) with KFLC index ≥ 5.9. In conclusion, Reiber's KFLC diagram shows a great diagnostic performance to detect an intrathecal KFLC production in patients with MS
Computed Tomography Versus Dacryocystography for the Evaluation of the Nasolacrimal Duct-A Study With 72 Patients.
No full textObjectives:In patients with epiphora, imaging of the nasolacrimal duct is essential not only for differential diagnosis, but also for preoperative planning. Advances in imaging technology and introduction of cone beam computed tomography (CB-CT) enable the combination of contrast agent-based imaging with a three dimensional tomography with low radiation exposure. However, the value of CT/CB-CT as an alternative to conventional dynamic dacryocystography (DCG) has not been evaluated yet. Study Design:Retrospective study. Methods:Conventional DCG was performed preoperatively in 72 consecutive patients treated for epiphora between 01/2013 and 04/2015 in our department. CB-CT or conventional CT was performed afterward with the contrast media still in place. Three separate experts (two radiologists and one otorhinolaryngologist) analyzed the radiographic images without any information about the respective clinical or surgical findings. The presence of further findings in the CT/CB-CT (eg, septal deviation, sinusitis) that were not detected in DCG and the overall visibility of the lacrimal duct system in both modalities were evaluated. Results:Good delineations of bone, soft tissue, and contrast agent in the lacrimal system were achieved with both methods. No side effects were noted. Beside the pathology of the lacrimal duct, CT/CB-CT scans enabled the additional diagnosis of pathologies in the nose and the sinus system in 65.7% of the patients. Accordance in the identified level of obstruction between the two modalities was achieved in 71.4% of the patients. Conclusion:Thus, CT/CB-CT should be used in conjunction with contrast agent to reliably identify the level of obstruction as preoperative standard and can be used as diagnostic tool in addition to or even instead of conventional DCG. Level of Evidence:4
Patient specific selection of lateral wall cochlear implant electrodes based on anatomical indication ranges
No full textRoot coverage using a connective tissue graft with epithelial striation in combination with enamel matrix derivatives - a long-term retrospective clinical interventional study.
Get PDFBACKGROUND:The application of a connective tissue graft with epithelial striation (CTG-ES) has been shown to improve the outcome of root coverage (RC) using the coronally advanced flap (CAF) and adjunctive administration of enamel matrix derivatives (EMD). Aim of the present study was to evaluate the long-term (mean: 16.19 ± 1.80 years, range: 13 to 18 years) stability of this treatment method with special focus on the location of the gingival margin and the width of keratinized tissue (WKT). METHODS:16 patients (10 female, 6 male, aged 35.36 ± 14.70 years at surgery) with 25 Miller class I or II gingival recession (GR) defects were treated using the CAF combined with the CTG-ES and EMD. The clinical measurements recorded at baseline (t0), 6 months (t1), and 13 to 18 years (t2) after surgery included recession depth (RED), probing pocket depth (PPD), clinical attachment level (CAL), and WKT. In addition, the number of sites with complete RC (CRC) and the mean RC (MRC) were documented at t1 and t2. The statistical analysis was performed using a linear mixed model. RESULTS:The RED (t0: 4.52 ± 1.56 mm; t1: 0.36 ± 0.76 mm; t2: 0.30 ± 0.60 mm) and CAL (t0: 6.16 ± 1.62 mm; t1: 1.86 ± 0.87 mm; t2: 1.54 ± 0.92 mm) were significantly reduced at t1 and t2 compared to t0 (p < 0.001). The PPD was significantly reduced at t2 compared to t0 (p = 0.016). The WKT (t0: 1.18 ± 1.28 mm; t1: 3.26 ± 0.98 mm; t2: 4.26 ± 1.83 mm) significantly increased from t0 to t1, from t0 to t2 (p < 0.001) and from t1 to t2 (p = 0.007). A CRC was recorded at 19 sites (76.0%) at t1 and t2. The MRC was 93.6 ± 12.8% at t1 and 93.3 ± 13.3% at t2. CONCLUSIONS:The use of the CAF combined with CTG-ES and EMD leads to stable long-term outcomes on teeth with Miller Class I or II GR defects. The CTG-ES represents a hybrid graft with increased position stability and advantageous properties for the healing process. We assume that the ES is responsible for the increase of the WKT
Neurological Immune Related Adverse Events Associated with Nivolumab, Ipilimumab, and Pembrolizumab Therapy-Review of the Literature and Future Outlook.
Get PDFImmune checkpoint inhibitor (ICI) therapy has revolutionized the management of various cancers with previously poor prognosis. Despite its great efficacy, the therapy is associated with a wide spectrum of immune-related adverse events (irAE) including neurological symptoms which can affect all parts of the central and peripheral nervous system. Even though these events are rare, they are of high relevance as the rate of residual symptoms or even fatal outcomes is remarkable. To provide a detailed overview of neurological adverse events associated with immune checkpoint-inhibitor therapy we conducted a literature search. While focusing on ipilimumab, nivolumab, and pembrolizumab therapy, all available case reports as well as larger case series and clinical trials have been considered. Eighty-two case reports about checkpoint-inhibitor therapy induced symptoms of the peripheral nervous system have been published, while only 43 case reports addressed central nervous system abnormalities. The frequency of immune checkpoint-inhibitor therapy inducing neurological adverse events is about 1% in larger studies. Especially neuromuscular adverse events exhibit distinct clinical and diagnostic characteristics. Additionally, several affected patients presented with overlap-syndromes, which means that symptoms and diagnostic findings indicating myositis, myasthenia gravis, and neuropathy were present in one individual patient at the same time. Thus, neurological and particularly neuromuscular adverse events of immune checkpoint-inhibitor therapy may constitute a new disease entity
Untersuchung der Marker der zirrhotischen Kardiomyopathie bei Kindern vor und nach Lebertransplantation
Get PDFImproved understanding of the pathophysiology and therapy of hearing impairment based on functional and molecular diagnostics using emission tomography
Get PDFAn experimental examination of cognitive processes and response inhibition in patients seeking treatment for buying-shopping disorder
No full textThere is an ongoing debate about whether buying-shopping disorder (BSD) should be acknowledged as a behavioral addiction. The current study investigated if mechanisms that play a prominent role in disorders due to substance use or addictive behaviors are relevant in BSD, particularly cue reactivity, craving, cognitive bias and reduced inhibitory control regarding addiction-relevant cues. The study included 39 treatment-seeking patients with BSD and 39 healthy control (HC) participants (29 women and 10 men in each group). Subjective responses toward buying/shopping-relevant visual cues were compared in patients vs. control participants. Experimental paradigms with neutral and semi-individualized buying/shopping-related pictures were administered to assess attentional bias, implicit associations and response inhibition with respect to different visual cues: Dot-probe paradigm (DPP), Implicit Association Task (IAT), Go/nogo-task (GNG). The severity of BSD, craving for buying/shopping, and symptoms of comorbid mental disorders (anxiety, depressive and hoarding disorders) were measured using standardized questionnaires. The BSD-group showed more general craving for buying/shopping, stronger subjective craving reactions towards buying/shopping-related visual cues, and more symptoms of anxiety, depression and hoarding disorder than control participants. Task performance in the DPP, IAT and GNG paradigm did not differ between the two groups. The present findings confirm previous research concerning the crucial role of craving in BSD. The assumption that attentional bias, implicit associations and deficient inhibitory control with respect to buying/shopping-related cues are relevant in BSD could not be proven. Future research should address methodological shortcomings and investigate the impact of acute psychosocial stress and present mood on craving responses, cognitive processing, and response inhibition in patients with BS