Förderverein Institut für Medizintechnik Dresden

AIMS: Clinical outcomes of patients with chronic heart failure (CHF) have improved, but evidence-based treatment appears to be imbalanced depending on patients' and physicians' gender. We aimed to determine the interactions of gender with medical treatment of CHF. METHODS AND RESULTS: Consecutive patients with CHF (n = 1857) were evaluated regarding co-morbidities, New York Heart Association classification, current medical treatment, and dosage of angiotensin-converting enzyme-inhibitors (ACE-Is) and beta-blockers. Gender of patients and treating physicians was recorded. Baseline characteristics of patients and physicians were comparable for males and females. Female patients were less frequently treated with ACE-Is, angiotensin-receptor blockers, or beta-blockers. Achieved doses were lower in female compared with male patients. Guideline-recommended drug use and achieved target doses tended to be higher in patients treated by female physicians. There was no different treatment for male or female patients by female physicians, whereas male physicians used significantly less medication and lower doses in female patients. In multivariable analysis, female gender of physicians was an independent predictor of use of beta-blockers. CONCLUSION: Treatment of CHF is influenced by patients', but also physicians' gender with regard to evidenced-based drugs and their dosage. Physicians should be aware of this problem in order to avoid gender-related treatment imbalances.

The COVID-19 pandemic has posed a serious threat to global mental health. Multiple lines of evidence suggest that there is a varying yet considerable increase in mental health issues among the general population and vulnerable groups. 1 2 The aftermath is obscure and speculative from a social, economic, individual and public mental health perspective. Recently published studies support the existence of an emotional epidemic curve, describing a high probability of an increase in the burden of mental health issues in the postpandemic era.3 4 Furthermore, previous major public health emergencies showed that more than half of the population developed mental health problems and required mental health intervention.4 5 There is, therefore, an urgent need to reorganise existing mental health services to address the current unmet needs for mental health and to prepare for future challenges in the postpandemic era in terms of prevention and management.

PURPOSE: Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of efficacy (tolerance), development of dependence, and the potential for drug abuse limit the clinical use of benzodiazepines (BZDs) for long-term treatment of epilepsy or anxiety. BZD ligands that are in current use act as full allosteric modulators of gamma-aminobutyric acid (GABA)-gated chloride channels and, on long-term administration, trigger a functional uncoupling between the GABAA and BZD recognition sites. Partial allosteric modulators, which have a low intrinsic activity at the BZD recognition site of the GABAA receptor, might eventually overcome the limitations of full agonists such as diazepam (DZP). METHODS: In the present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former name AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures. RESULTS: ELB 138 was shown to increase potently the pentylenetetrazole (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ dog model. To study whether physical dependence developed during long-term treatment, the BZD antagonist flumazenil was injected after 5 weeks of treatment with ELB 138. Compared with prolonged treatment with DZP, only relatively mild abstinence symptoms were precipitated in dogs treated with ELB 138, particularly at the lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity without significant difference to standard treatments (phenobarbital or primidone) but was much better tolerated than the standard drugs. In dogs with chronic epilepsy, most dogs exhibited a reduction in seizure frequency and severity during add-on treatment with ELB 138. CONCLUSIONS: The data demonstrate that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant efficacy without tolerance in a dog seizure model as well as in epileptic dogs with spontaneously recurrent seizures. These data thus substantiate that partial agonism at the BZD site of GABAA receptors offers advantages versus full agonism and constitutes a valuable approach for treatment of seizures.

Calcium phosphate cements (CPCs) are widely used for bone-defect treatment. Current developments comprise the fabrication of porous scaffolds by three-dimensional plotting and doting using biologically active substances, such as strontium. Strontium is known to increase osteoblast activity and simultaneously to decrease osteoclast resorption. This study investigated the short- and long-term in vivo performances of strontium(II)-doted CPC (SrCPC) scaffolds compared to non-doted CPC scaffolds after implantation in unloaded or load-bearing trabecular bone defects in sheep. After 6 weeks, both CPC and SrCPC scaffolds exhibited good biocompatibility and osseointegration. Fluorochrome labeling revealed that both scaffolds were penetrated by newly formed bone already after 4 weeks. Neither strontium doting nor mechanical loading significantly influenced early bone formation. In contrast, after 6 months, bone formation was significantly enhanced in SrCPC compared to CPC scaffolds. Energy dispersive X-ray analysis demonstrated the release of strontium from the SrCPC into the bone. Strontium addition did not significantly influence material resorption or osteoclast formation. Mechanical loading significantly stimulated bone formation in both CPC and SrCPC scaffolds after 6 months without impairing scaffold integrity. The most bone was found in SrCPC scaffolds under load-bearing conditions. Concluding, these results demonstrate that strontium doting and mechanical loading additively stimulated bone formation in CPC scaffolds and that the scaffolds exhibited mechanical stability under moderate load, implying good clinical suitability. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:106-117, 2018.

Abstract Eine neuartige Xanthin‐Synthese wird beschrieben. Ausgangsstoffe sind an der 4‐Amino‐gruppe monosubstituierte 5‐Nitroso‐uracilderivate ( 3 ). Diese spalten beim Erhitzen intramolekular Wasser ab unter Bildung der Xanthine 4 . Durch Oxydationsmittel entstehen aus den Nitrosouracilderivaten 3 zunächst Azomethine 12 , die sich zu 7‐Hydroxy‐xanthinen 13 cyclisieren.

Abstract Die Existenz eines löslichen, kristallisierten Oligomeren [HSi(O 1/2 ) 3 ] 8 wurde wahrscheinlich gemacht.

Fragaria vesca is the most distributed wild species in the genus Fragaria. Due to this biogeography a high diversity is to expect. During two harvest seasons sixteen accessions from different locations from the most eastern habitat at Lake Baikal in Siberia, from Middle and Southern Europe and Northern Europe with Scandinavia and Iceland were investigated as well as two of the three described North American subspecies and three F. vesca cultivars. Five very distinct European F. ×ananassa cultivars were chosen to serve as a comparison. Beside brix value and acid contents the aroma patterns including 67 volatile compounds were quantified by stir bar sorptive extraction followed by gas chromatography with mass spectrometric detection. The diversity of important volatiles of Fragaria vesca and F. ×ananassa is discussed regarding biogeography, domestication, breeding and the so-called funnel effect.

While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany.

Abstract Mit wäßrigen Flußsäure‐ bzw. wäßrigen Fluoridlösungen lassen sich die bei direkter Synthese anfallenden Organochlorsilane als ‐fluorsilane trennen, da das SiCl 4 in H 2 SiF 6 übergeht und die trifunktionellen Verbindungen aus wäßriger Lösung als Salze der Alkyl‐bzw. Arylpentafluorokieselsäure an‐ bzw. ausfallen. Die mono‐ und difunktionellen Organofluorsilane bilden keine Komplexe. Sie bleiben nach Durchleiten durch die wäßrigen Fluoridlösungen unverändert gasförmig. Die wäßrigen Lösungen der Salze der Organopentafluorokieselsäuren geben mit Schwermetallsalzen die farbigen Alkyle bzw. Aryle der Metalle. Lösungen von AgNO 3 + NH 1 F usw. sind Reagenzien auf monoalkyliertes bzw. ‐aryliertes Silizium.

Abstract Die Synthese von 8.8‐disubstituierten 8 H ‐Xanthinen 2 , durch Dehydratisierung von 4‐Amino‐5‐nitroso‐uracilderivaten 1 , deren Aminogruppe durch einen Rest —CHRR′ substituiert ist, wird beschrieben. Durch Oxydationsmittel werden die Nitrosouracilderivate 1 zu 8 H ‐Xanthin‐7‐ N ‐oxiden 4 , dehydriert. Diese isomerisieren sehr leicht zu 3 H ‐Pyrimido[5.4‐ c ]‐1.2.5‐oxadiazinen 5 . Die 8.8‐disubstituierten 8 H ‐Xanthine 2 können in 7.8‐disubstituierte Xanthine 11 umgelagert werden.

Background: Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP. Methods: Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[ 18 F]fluoro- D -glucose (K iS ), and its difference between the two PET/CT was calculated (ΔK iS ). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure–volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation. Results: Normalized 18 F-FDG uptake rate increased significantly from first to second PET/CT ( p = 0.012). ΔK iS significantly correlated with median MP (ρ = 0.738, p = 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h ( p = 0.012, p = 0.036, and p = 0.025, respectively). Resistance and PaCO 2 were significantly higher ( p = 0.012 and p = 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention. Conclusions: In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP.

Abstract Die Herstellung von Alloxazinderivaten ( 3 ) und ihren 5‐ N ‐Oxiden ( 4 ) durch Nitrosierung von 4‐Anilino‐uracil‐Derivaten wird beschrieben. Die Alloxazin‐5‐ N ‐oxide können durch fraktionierte Kristallisation abgetrennt oder zu den entsprechenden Alloxazinen reduziert werden.

Norovirus (NV) is a major cause of gastroenteritis worldwide. Antivirals against such important pathogens are on demand. Among the viral proteins that orchestrate viral replication, RNA-dependent-RNA-polymerase (RdRp) is a promising drug development target. From an in silico-docking search focused on the RdRp active site, we selected the compound PPNDS, which showed low micromolar IC50vs. murine NV-RdRp in vitro. We report the crystal structure of the murine NV-RdRp/PPNDS complex showing that two molecules of the inhibitor bind in antiparallel stacking interaction, properly oriented to block exit of the newly synthesized RNA. Such inhibitor-binding mode mimics two stacked nucleotide-bases of the RdRp/ssRNA complex.

Abstract G. Fritz und J. Grobe beschreiben eine linear gebaute Verbindung (C 6 H 16 Si 2 ) mit einer Si‐ C‐Doppelbindung, (CH 3 ) 2 Si; CH. Si(CH 3 ) 3 , die sie aus Pyrolyseprodukten des Si(CH 3 ( 4 gewonnen haben. Es wurde eine Verbindung mit der gleichen Zusammensetzung und den gleichen physikalischen und chemischen Eigenschaften erhalten, der auf Grund ihrer Darstellung aus Brommethyl‐ dimethyl‐chlorsilan und Magnesium jedoch Vierring‐Struktur (VI) ohne Doppelbindung zukommen muß.

There is an increasing movement toward international collaboration and global discussion in mental health. If provided with the right opportunities, early career psychiatrists (ECPs) and researchers in mental health can contribute meaningfully to this discussion. However, they often experience multiple barriers when attempting to add their voices via academic publications. We represent a diverse group of ECPs and researchers from all six World Health Organization regions. In this piece, we discuss these barriers, grounded in our first-hand experiences, and put forth a series of recommendations. The most potentially beneficial and immediate way forward is ensuring a much-needed mentorship and support, particularly for low- and middle-income countries. In this regard, international organizations, especially those with a particular focus on education, such as the Section on Education in Psychiatry of the World Psychiatric Association, can play a pivotal role.

Abstract Molekelmassenspektren positiver sowie negativer Ionen stützen die Annahme, daß bei Organotriptych‐siloxazolidinen (Silatranen) zwischen dem Stickstoff und dem dadurch pentacovalenten Silicium eine koordinativ‐covalente Bindung besteht. Mit den Alkyl‐ und Arylverbindungen können Silber‐Alkyle und‐Aryle dargestellt werden, die aber rasch unter Abscheidung von elementarem Silber zerfallen. Die Alkoxyverbindungen ergeben mit Silbernitrat dagegen zunächst Silberoxid. Mit Hilfe der Organo‐triptychsiloxazolidine lassen sich aber beständige Organoquecksilber‐, ‐antimon‐, ‐wismut‐und ‐bleiverbindungen darstellen.

Abstract Einfache stark hydrolyseempfindliche Methylchlorsilane und ‐silanole werden über raschenderweise von wäßrigen Antimontrifluoridlösungen fast ebenso gut fluoriert wie von der wasserfreien Verbindung. Methylchlordisiloxane werden zwar von verdünnter Flußsäure, dagegen nicht von wäßriger Antimontrifluoridlösung gespalten. Der Fluorierung der SiCl‐Bindung geht offenbar die Hydrolyse zum Silanol voraus. Der Einfluß von Bortrifluorid‐dihydrat auf die Fluorierung in wäßriger Antimontrifluoridlösung wird untersucht. Im Gegensatz zur SiCl‐ wird die CCl‐Bindung von wäßriger Antimontrifluoridlösung nicht, von 20− bis 40proz. Flußsäure bei Raumtemperatur merklich fluoriert.

Adenosine is an endogenous nucleoside that is released under pathological conditions and interacts with four G-protein-coupled receptor subtypes. These receptors are widely distributed throughout the body. They are involved in many central and peripheral processes, including immunological and inflammatory responses. In inflammatory and asthmatic conditions, the extracellular concentration of adenosine increases in the airway tissue. It enhances mast cell degranulation and bronchoconstriction, but may also inhibit eosinophil or lymphocyte function or modulate reactive oxygen species generation in neutrophils. Despite a large number of studies clearly indicating the effects of adenosine in vitro, many aspects of the mechanisms involved in the adenosine-mediated responses are still unclear, and our knowledge is limited in understanding the complex multifactorial interactions occurring in the whole body. The discovery of adenosine receptor compounds acting with increasing selectivity will bring new approaches to the use of adenosine receptor agonists and antagonists and may clarify some of the current uncertainties. On the basis of our present knowledge, the development of adenosine A(2A)- or (A3)-receptor agonists as antiinflammatory agents or A(2B)-receptor antagonists as inhibitors of mast cell degranulation for the treatment of asthma holds promise.

Bergmeier, E., Kypriotakis, Z., Jahn, R., Böhling, N., Dimopoulos, P., Raus, Th. & Tzanoudakis, D.: Flora and phytogeographical significance of the islands Chrisi, Koufonisi and nearby islets (S Aegean, Greece). — Willdenowia 31: 329–356. 2001. — ISSN 0511-9618.An annotated floristic catalogue is provided for the islands Chrisi (Gaidouronisi), Koufonisi and the nearby islets Mikronisi, Strongili, Makrouli and Trachilos, all off SE Kriti. Critical use is made of literature data, and hitherto unpublished records, mostly from 1997 through 2000, add substantially to the first full vascular plant inventory of the islands. The total numbers of vascular plant taxa currently known from each island are as follows (accepted taxon records from literature, if extant, in brackets): Chrisi 275 (162), Mikronisi 71 (21), Koufonisi 273 (71), Strongili 110, Makrouli 115, Trachilos 96. Most noteworthy are Suaeda palaestina and Ononis vaginalis (currently with their single localities in Europe); Allium brachyspathum, Astragalus boeticus, A. peregrinus, Galium recurvum, Hippocrepis unisiliquosa, Lagurus ovatus subsp. nanus, Ononis diffusa, Orobanche grisebachii, Schoenoplectus litoralis (new records or confirmations for the Cretan area as a whole, or for the territory of Kriti proper including offshore islands); and Chlamydophora tridentata, Frankenia corymbosa and Hymenolobus procumbens (new regional records for the E part of Kriti and its offshore islands). The N African, pronouncedly thermophilous phytogeographical element is fairly well represented in the investigated area, thence Koufonisi in particular must be considered the driest and hottest SE European island. The principal habitats encountered in each of the islands are outlined and the present conditions for nature conservation discussed.

From the bloodsucking bug Dipetalogaster maximus, a protein with anticoagulant activity was isolated and biochemically characterized. The isolated protein, named dipetalogastin, possesses an average molecular mass of 11.8 kD. Its N-terminal sequence shows homology to rhodniin, a thrombin inhibitor isolated from the bug Rhodnius prolixus. The in vitro anticoagulant activity of dipetalogastin occurs via the inhibition of thrombin. The anticoagulant and thrombin inhibitory potency of dipetalogastin is comparable to that of recombinant hirudin. Its specific thrombin inhibitory activity is 9,300 antithrombin units/mg protein. Dipetalogastin forms only 1:1 molar complexes with thrombin. It is a tight-binding inhibitor of thrombin possessing a dissociation constant of 125 fM. It does not inhibit factor Xa or alpha-chymotrypsin and only weakly inhibits trypsin.