Analysis of the structure and function of the epidermal barrier in patients with ichthyoses-clinical and electron microscopical investigations.

BACKGROUND: Ichthyoses are pathogenetically characterized by a pronounced disorder of the epidermal barrier. Clinically, hyperkeratosis, severe scaling and erythroderma are present on the entire integument. The time-consuming therapy includes daily baths and the application of skin care products to restore the epidermal barrier. OBJECTIVES AND METHODS: To enhance the knowledge about the structure and function of the epidermal barrier in ichthyoses, we conducted clinical, biophysical and electron microscopical measurements on 46 patients with ichthyoses, including autosomal recessive ichthyoses, keratinopathic ichthyoses, X-chromosomal-recessive ichthyosis and Netherton syndrome. RESULTS: The patients displayed a significantly decreased skin hydration along with unexpectedly low transepidermal waterloss values. Electron microscopical examinations demonstrated a severe occlusion of the epidermis by lipid remnants of skin care products in the stratum corneum. We found decreased intercellular lipid lamellae and an increased undulation of the corneocyte membrane of all ichthyoses, mostly pronounced in Netherton syndrome. The lipid profiles of ichthyoses showed decreased esterified Ω-hydroxy-sphingosine (EOS) ceramide levels. CONCLUSIONS: The results demonstrate the extent of the epidermal barrier disruption in ichthyoses. In combination with the knowledge about pathogenetic causes, individually improved therapeutic options can be derived from our results. In the future, the analyses of the organization of intercellular lipid lamellae and corneocyte membrane undulation will enable improved investigations of the epidermal barrier in ichthyoses and may be used to study and evaluate possible effects of topical skin preparations.

[Risk stratification of emergencies during the COVID-19 pandemic within the emergency department]. / Risikostratifizierung von Notfällen während der COVID-19-Pandemie in der Zentralen Notaufnahme.

BACKGROUND: The COVID-19 pandemic represents a complex challenge for medical staff within emergency departments (ED) of hospitals at all care levels. Beside regular emergency care, rapid detection and isolation of COVID-19 cases are obligatory for prevention of internal viral transmission and efficient medical staff protection. METHODS: In this study a model of risk stratification for suspected SARS-CoV­2 and COVID-19 cases was developed on the basis of epidemiologic criteria of the Robert-Koch Institute including five risk categories (RC). The model was implemented in a hospital of basic and regular care level. By combination of risk categories with specific isolation, hygienic and personal protection procedures all areas of the ED were restructured. In a retrospective study all inpatient cases (n = 491) were re-evaluated during a 4-week interval (26 March-26 April 2020). RESULTS: In the study population 25 SARS-CoV­2 positive cases (5.2%) were identified. These cases were categorized according to the risk stratification model as follows: RC I-confirmed SARS-CoV­2 infection 36% (n = 9), RC II-reasonable suspected cases 32% (n = 8), RC III-differential diagnostic cases 12% (n = 3), RC IV-low probability 8% (n = 2) and RC V-no evidence 12% (n = 3). No viral transmission was detected during the whole period within medical staff and patients of the ED. CONCLUSIONS: Introduction of COVID-19 risk categories within the ED permits central control of important hygienic processes with respect to SARS-CoV­2 infection probability. By continuous re-evaluation of case definitions local outbreaks can be used to adapt criteria within the risk categories. Risk stratification of COVID-19 cases allows for a strict separation of COVID-19 and non-COVID-19 emergencies and thus ensures effective infection prevention of medical staff and patients.

Humans Predict Action using Grammar-like Structures.

Efficient action prediction is of central importance for the fluent workflow between humans and equally so for human-robot interaction. To achieve prediction, actions can be algorithmically encoded by a series of events, where every event corresponds to a change in a (static or dynamic) relation between some of the objects in the scene. These structures are similar to a context-free grammar and, importantly, within this framework the actual objects are irrelevant for prediction, only their relational changes matter. Manipulation actions and others can be uniquely encoded this way. Using a virtual reality setup and testing several different manipulation actions, here we show that humans predict actions in an event-based manner following the sequence of relational changes. Testing this with chained actions, we measure the percentage predictive temporal gain for humans and compare it to action-chains performed by robots showing that the gain is approximately equal. Event-based and, thus, object independent action recognition and prediction may be important for cognitively deducing properties of unknown objects seen in action, helping to address bootstrapping of object knowledge especially in infants.

Non-ambulatory dogs with cervical intervertebral disc herniation: single versus multiple ventral slot decompression.

OBJECTIVE: To evaluate the proportion of non-ambulatory dogs with cervical intervertebral disc herniation (IVDH) in a private clinic and to compare signalment and outcome between those that underwent single or multiple ventral slot decompression (VSD). DESIGN: Retrospective cohort study. METHODS: After screening 43,378 medical records (January 2010-September 2016), those of 185 dogs with non-ambulatory tetraparesis or tetraplegia along with cervical IVDH that had undergone single (123) or multiple (62) VSD were included in this study. Data on signalment, preoperative neurological status, location of affected intervertebral disc(s), time to ambulation and short-term outcome were compared between single and multiple VSD groups. RESULTS: The proportion of non-ambulatory dogs with IVDH was 35.3%. The prevalence of non-ambulation was higher in male dogs (0.56%) than in female dogs (0.26%; P < 0.001) and in neutered dogs than in unneutered dogs (0.51% and 0.27%, respectively, P < 0.001). After surgery, 96.2% of the dogs reached ambulatory status. Dogs with multiple IVDH were older than those with single IVDH. Sex, neutering status or size did not affect the outcome or ambulation status postsurgery. The Pekingese was the most commonly affected breed in both groups. There was no difference in the time to reach ambulation and the presence of neurological deficits after surgery between dogs that underwent single and multiple VSD. CONCLUSIONS: In this cohort, dogs undergoing multiple VSD had a good postoperative outcome, and their short-term functional recovery was equal to that of dogs undergoing single ventral slot compression.

[Model project on interdisciplinary university teaching-medical and psychology students learn together for the first time]. / Modellprojekt zur interdisziplinären universitären Lehre ­ Studierende der Medizin und der Psychologie lernen erstmals gemeinsam.

An interdisciplinary collaboration is required in the medical care of chronically ill patients with complex illnesses. Especially in the field of internistic rheumatology, interdisciplinary work is essential to consider the complex somatic and psychosocial aspects of a chronic illness. Nevertheless, the aspects of interprofessional work in the study of medicine and psychology are insufficiently addressed. For this reason, a model project for interdisciplinary university teaching was conceived, which combines both subjects. The course was held for the first time in semester 2019/2020 and was rated excellent by the participants. The main goal of the course is the implementation of interprofessional work in the training of medical personnel. In addition, the discipline of internistic rheumatology could be brought closer to the students.

A plant oil-containing pH 4 emulsion improves epidermal barrier structure and enhances ceramide levels in aged skin.

OBJECTIVE: Xerosis is a serious problem among the very old. It is a dermatological challenge caused by significant alterations in stratum corneum (SC) function and structure. Two negative changes in aged skin are (i) the enhanced skin surface pH and (ii) the altered SC lipid content, composition and ordering. METHODS: Therefore, we investigated the way in which an acidic skin care product with different plant oils affects SC function, structure and lipid profile in older subjects with dry skin. Before and after a 3-week application period, different biophysical measurements were performed: transepidermal water loss, SC hydration and skin surface pH. In addition, the SC lipid matrix was evaluated by analysis of the intercellular lipid lamellae and the SC lipid profile. RESULTS: After treatment, a significant increase in lipid lamellae in the intercellular space of the SC was observed in the area treated with the test product compared to the untreated area. Furthermore, the ceramide level was found to be increased, although ceramides were not provided by the acidic test formulation. CONCLUSION: In summary, topical application of a pH 4.0 product containing plant oils improves epidermal barrier formation and SC lipid ordering and ratio in aged dry skin.

Impact of plant growth-promoting rhizobacteria on root colonization potential and life cycle of Rhizophagus irregularis following co-entrapment into alginate beads.

AIMS: This study aimed at evaluating the impact of seven plant growth-promoting rhizobacteria (PGPR) on root colonization and life cycle of Rhizophagus irregularis MUCL 41833 when co-entrapped in alginate beads. METHODS AND RESULTS: Two in vitro experiments were conducted. The first consisted of the immobilization of R. irregularis and seven PGPR isolates into alginate beads to assess the effect of the bacteria on the pre-symbiotic growth of the fungus. In the second experiment, the best performing PGPR from experiment 1 was tested for its ability to promote the symbiotic development of the AMF in potato plantlets from three cultivars. Results showed that only one isolate identified as Pseudomonas plecoglossicida (R-67094) promoted germ tube elongation and hyphal branching of germinated spores during the pre-symbiotic phase of the fungus. This PGPR further promoted the symbiotic development of the AMF in potato plants. CONCLUSIONS: The co-entrapment of Ps. plecoglossicida R-67094 and R. irregularis MUCL 41833 in alginate beads improved root colonization by the AMF and its further life cycle under the experimental conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Co-entrapment of suitable AMF-PGPR combinations within alginate beads may represent an innovative technology that can be fine-tuned for the development of efficient consortia-based bioformulations.

[Aortic valve replacement in the elderly]. / Aortenklappenersatz im Alter.

The treatment of severe symptomatic aortic valve stenosis by conventional aortic valve replacement (AVR) or by transcatheter aortic valve implantation (TAVI) has a good perinterventional prognosis even for patients of advanced age. Having a heart team select the best management strategies based on current guidelines for each individual patient is essential for success. Especially in elderly and increasingly multimorbid patients with sometimes severe preconditions, the detection of functional deficits is relevant not only for the mortality but also for perioperative and postoperative complications as well as the functional outcome. Various methods of geriatric assessment are important supplements to standard risk scores. The aim is to implement targeted interventions to minimize the risk factors and to improve the prognosis for elderly patients. The aim of this article is to provide an overview of the current therapy options for aortic valve replacement and to summarize current aspects of treatment options for elderly patients.

First experience with the new Sorin Crown PRT bioprosthetic aortic valve: early postoperative outcome and hemodynamic performance in 90 patients.

AIM: The Crown PRT (The Phospholipid Reduction Treatment) is a new stent bovine bioprosthesis for aortic valve replacement (AVR). Aim of this paper is to report the postoperative clinical and hemodynamic results after ninety consecutive implants. METHODS: After receiving CE mark in July 2014, two European university centers implanted the new Crown PRT (Sorin Group, Burnaby, Canada) for the first time. Up to now, ninety patients underwent aortic valve replacement, in isolated or combined procedures, for aortic stenosis or insufficiency. Intraoperative transesophageal echocardiogram was used to assess the prosthesis's function. In hospital outcomes and echocardiographic parameters were recorded. RESULTS: Age and Log Euroscore were 71.8±7.9 years and 10.2%±4.5 respectively. In-hospital mortality for isolated AVR was 0%; one patient died after a multiple procedure (overall 30-days mortality 1.1%). No adverse device effects were recorded. Intensive Care Unit stay was 2±5.8 days. At discharge, echocardiogram showed no paravalvular leaks and normal postoperative gradients. CONCLUSION: Our starting results showed that the Crown PRT is safe and reliable, with excellent hemodynamic performance. Further clinical results with a larger population and long term follow-up are needed to assess the versatility and the durability of this new device.

Femtosecond all-optical synchronization of an X-ray free-electron laser.

Many advanced applications of X-ray free-electron lasers require pulse durations and time resolutions of only a few femtoseconds. To generate these pulses and to apply them in time-resolved experiments, synchronization techniques that can simultaneously lock all independent components, including all accelerator modules and all external optical lasers, to better than the delivered free-electron laser pulse duration, are needed. Here we achieve all-optical synchronization at the soft X-ray free-electron laser FLASH and demonstrate facility-wide timing to better than 30 fs r.m.s. for 90 fs X-ray photon pulses. Crucially, our analysis indicates that the performance of this optical synchronization is limited primarily by the free-electron laser pulse duration, and should naturally scale to the sub-10 femtosecond level with shorter X-ray pulses.

BH3-Only protein bmf is required for the maintenance of glucose homeostasis in an in vivo model of HNF1α-MODY diabetes.

Heterozygous loss-of-function mutations in the hepatocyte nuclear factor 1α (HNF-1α) gene can lead to diminished amounts of functional HNF-1α, resulting in the onset of a particularly severe form of maturity-onset diabetes of the young (MODY). We have previously shown that induction of a dominant-negative mutant of HNF-1α (DNHNF-1α) results in the activation of the bioenergetic stress sensor AMP-activated protein kinase (AMPK), preceding the onset of apoptosis and the induction of pro-apoptotic Bcl-2 homology domain-3-only protein Bmf (Bcl-2-modifying factor) as a mediator of DNHNF-1α-induced apoptosis. Through the knockout of bmf in a transgenic mouse model with DNHNF-1α suppression of HNF-1α function in pancreatic beta-cells, this study aimed to examine the effect of loss-of-function of this BH3-only protein on the disease pathology and progression, and further elucidate the role of Bmf in mediating DNHNF-1α-induced beta-cell loss. Morphological analysis revealed an attenuation in beta-cell loss in bmf-deficient diabetic male mice and preserved insulin content. Surprisingly, bmf deficiency was found to exacerbate hyperglycemia in both diabetic male and hyperglycemic female mice, and ultimately resulted in a decreased glucose-stimulated insulin response, implicating a role for Bmf in glucose homeostasis regulation independent of an effect on beta-cell loss. Collectively, our data demonstrate that Bmf contributes to the decline in beta-cells in a mouse model of HNF1A-MODY but is also required for the maintenance of glucose homeostasis in vivo.

[Services for the early recognition of psychoses and bipolar disorders in Germany: inventory survey study]. / Angebote zur Früherkennung von Psychosen und bipolaren Störungen in Deutschland: Bestandsaufnahme.

BACKGROUND: In order to successfully implement early recognition and intervention services in psychiatry, it is crucial to improve the attention to and recognition of severe mental disorders and to establish low threshold services that are available at short notice for diagnostic and treatment procedures. MATERIAL AND METHODS: For this inventory survey study, questionnaires regarding the presence and type of early recognition services for psychoses and bipolar disorders were sent separately to German psychiatric hospitals by mail in September and October 2012. Additionally, an internet search and telephone inquiries as well as an alignment of responses from the two surveys and with network lists from published and ongoing early recognition studies were performed. RESULTS: Response rates in the psychosis and bipolar disorder surveys were 21 % (51/246) and 36 % (91/255), respectively. Three quarters of participating institutions reported at least an interest in creating an early recognition service for psychoses and one half for bipolar disorders. Overall, 26 institutions were identified that already offer early recognition of psychoses and 18 of bipolar disorders. Of these 16 are low threshold early recognition centres with direct access at short notice for first-episode patients and person from at-risk groups and separate specific public relations work. Of these early recognition centres five have a separate and easy to find homepage available; in an additional 15 institutions the specific websites are part of the institutions homepage. CONCLUSION: Despite widespread interest and the increasingly recognized importance of early recognition and intervention services in psychiatry, there is currently no nationwide coverage with early recognition services for severe mental disorders in Germany. Public relations and information activities are not (yet) sufficiently provided to reach affected persons and their environment. Common standards are (still) missing and interdisciplinary models are sparse. To correct these shortcomings, amongst other factors, acquisition of sufficient funding for such services is required.

Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm(®) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622).

BACKGROUND: Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. OBJECTIVE: We conducted the first clinical trial with the novel PlasmaDerm® VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. METHODS: From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak® , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). RESULTS: The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION: Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.

Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury.

Stress signaling in response to oxygen/glucose deprivation (OGD) and ischemic injury activates a group of pro-apoptotic genes, the Bcl-2 homology domain 3 (BH3)-only proteins, which are capable of activating the mitochondrial apoptosis pathway. Targeted studies previously identified the BH3-only proteins Puma, Bim and Bid to have a role in ischemic/hypoxic neuronal injury. We here investigated the transcriptional activation of pro-apoptotic BH3-only proteins after OGD-induced injury in murine neocortical neurons. We observed a potent and early upregulation of noxa at mRNA and protein level, and a significant increase in Bmf protein levels during OGD in neocortical neurons and in the ipsilateral cortex of mice subjected to transient middle cerebral artery occlusion (tMCAO). Surprisingly, gene deficiency in noxa reduced neither OGD- nor glutamate-induced neuronal injury in cortical neurons and failed to influence infarct size or neurological deficits after tMCAO. In contrast, bmf deficiency induced significant protection against OGD- or glutamate-induced injury in cultured neurons, and bmf-deficient mice showed reduced neurological deficits after tMCAO in vivo. Collectively, our data not only point to a role of Bmf as a BH3-only protein contributing to excitotoxic and ischemic neuronal injury but also demonstrate that the early and potent induction of noxa does not influence ischemic neuronal injury.

[Nellix® endovascular aneurysm sealing (EVAS) - a new technology for endovascular management of infrarenal aortic aneurysms]. / Nellix® Endovascular Aneurysm Sealing (EVAS) - eine neue Technologie zur endovaskulären Ausschaltung infrarenaler Aortenaneurysmen.

BACKGROUND: Recently used endografts for envascular aneurysm repair (EVAR) exclude the pathology by fixation at both the proximal and distal landing zone. Due to endoleaks and migration EVAR is associated with a relevant rate of secondary interventions. The Nellix® system (Endologix Inc., CA, USA) was developed to seal the complete aneurysm using a polymer filling, therefore stabilising endograft-position and reducing the rate of endoleaks and reinterventions. The present contribution introduces the method, describes the technique of implantation and presents the first clinical results. Material und Methods: The Nellix system consists of two balloon-expandable stent grafts made of a cobalt-chromium composition, surrounded with ePTFE and the so-called endobags. During the implantation each endobag is filled with a non-biodegradable polymer, sealing the aneurysm lumina including the proximal and distal landing zone. Hence, lumbar arteries will be sealed to reduce the probability of a type II endoleak. RESULTS: Longterm durability as well as the structural integrity of the Nellix system has been proven over 4 years in sheep experiments. The technical success in a multicentre, prospective registry was 94% without the appearance of severe adverse events (migration, occlusion, secondary endoleak). CONCLUSION: EVAS is a new and different concept of endovascular AAA repair. Recent clinical data of the Nellix system are promising showing a high technical success rate while the need for secondary intervention is low. Further studies in larger cohorts are needed.

Sternal wound dehiscence from intense coughing in a cardiac surgery patient: could it be prevented?

This case report is on a obese patient who underwent a coronary artery bypass. The immediate postoperative phase, on the 8th day, was characterized by sternal dehiscence with diastasis, from intense coughing. At present, for obese patients there are not any guidelines aimed to prevent the sternal diastasis. The use of a sternum support vest after median sternotomy could be a valuable tool in the postoperative care of our patients, in order to avoid chest wall hyperexpansion and to prevent sternal wound dehiscence and diastasis.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.