N-Heterocyclic Olefins on a Silicon Surface.

The adsorption of N-heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The adsorption geometry strongly depends on the N-substituents: for large N-substituents, an upright adsorption geometry is favored, while a flat-lying geometry is found for the NHO with smaller wingtips. These different geometries strongly influence the quality and properties of the obtained monolayers. The upright geometry leads to the formation of ordered monolayers, whereas the flat-lying NHOs yield a mostly disordered, but denser, monolayer. The obtained monolayers both show large work function reductions, as the higher density of the flat-lying monolayer is found to compensate for the smaller vertical dipole moments. Our findings offer new prospects in the design of tailor-made ligand structures in organic electronics and optoelectronics, catalysis, and material science.

New Members of the Cinchona Alkaloids Family: Assembly of the Triazole Heterocycle at the 6' Position.

The substance class of the well-known Cinchona alkaloids is widened by 6'-Amino-cinchonine and 6'-Amino-cinchonidine, novel compounds which incorporate a primary amino function in the quinolinic ring system. These key intermediates open the field for a range of fruitful chemistry. Here is described a short and direct pathway for the synthesis of triazole containing derivatives of the above-mentioned substances using the [3 + 2] Huisgen cycloaddition. For this purpose, the amines were first converted into the corresponding azides. Based on this, non-substituted and silyl-protected triazoles were synthesized as examples. Furthermore, didehydrated derivatives of quincorine and quincoridine were used as addition partners, resulting in compounds that carry the quinuclidine ring of the cinchona alkaloids at both ends. Some of these compounds were examined radiographically to investigate the position of the quinuclidine ring to the triazole. The solid-state structures of compounds 10, 11 and 28 were determined by X-ray diffraction analyses.

Rapid responding to the COVID-19 crisis: Assessing the resilience in the German restaurant and bar industry.

The COVID-19 pandemic has fundamentally impacted the restaurant and bar industry. Simultaneously, this industry is already undergoing structural change. Using the concept of organisational resilience, we analyse the impact of the COVID-19 crisis on owner's assessment of resilience in the German restaurant and bar industry. Findings from an online survey with 623 owners and managers show that ex-ante business problems, and financing by loans or credit, reduce the likelihood of owners perceiving their business as resilient; while, delivery and takeaway service, ownership of property and higher age of owners, increase the likelihood of enterprise resilience. The paper contributes to understanding how restaurants and bars absorb and cope with the COVID-19 crisis. Furthermore, we make recommendation for future research on the recovery and adaptability of the business sector.

[Management of intra-abdominal dysgerminoma During pregnancy - A Case Report and Literature Review]. / Management Unterbauchraumforderungen in der Schwangerschaft ­ Fallbeschreibung eines extraovariell-intraabdominalen Dysgerminoms mit Überblick über die Literatur.

INTRODUCTION: Dysgerminomas are rare malignant germ cell tumors. They usually arise from the ovary, but case reports describing extraovarian dysgerminomas do exist. When treated adequately the disease has a good prognosis. Dysgerminomas diagnosed during pregnancy are very rare. METHODOLOGY: Report of extraovarian intra-abdominal dysgerminoma during pregnancy. Systematic literature review. CASE REPORT: A 35-year-old second gravida was diagnosed with a suspected intra-abdominal mass at 20 gestational weeks. During an exploratory laparotomy, a tumor infiltrating the transverse colon and histologically identified as a dysgerminoma was resected. Ovaries were clinically unremarkable. The induction of chemotherapy was postponed until after delivery. At 34 gestational weeks the patient underwent cesarean section and tumor debulking. Four cycles of bleomycin, etoposide and cisplatin were administered. After 12 months, cystic ovaries were found. Hysterectomy with bilateral adnexectomy was performed but no malignancy found. After 16 months, the patient was still in complete remission. CONCLUSION: We describe the first-ever published dysgerminoma in gravida primarily evolving intraabdominally and not affecting the ovaries. The decision for cytoreductive surgery, prolongation of pregnancy and postponing chemotherapy until after delivery combined the best benefit for the baby with a good maternal prognosis. Due to limited data regarding dysgerminomas in pregnancy, individual interdisciplinary concepts are mandatory.

The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation.

Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA-mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration. Furthermore, ADAM8 promotes αL-integrin upregulation and THP-1 cell adhesion to endothelial cells. On endothelial cells ADAM8 enhances transendothelial migration and increases cytokine-induced permeability. On epithelial cells the protease facilitates migration in a wound closure assay but does not affect transepithelial leukocyte migration. Blood leukocytes and bone marrow-derived macrophages (BMDM) from ADAM8-deficient mice show suppressed chemotactic response. Intranasal application of LPS to mice is accompanied with ADAM8 upregulation in the lung. In this model of acute lung inflammation ADAM8-deficient mice are protected against leukocyte infiltration. Finally, transfer experiments of BMDM in mice indicate that ADAM8 exerts a promigratory function predominantly on leukocytes. Our study provides in vitro and in vivo evidence that ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment.

CXCL10 triggers early microglial activation in the cuprizone model.

A broad spectrum of diseases is characterized by myelin abnormalities and/or oligodendrocyte pathology. In most, if not all, of these diseases, early activation of microglia occurs. Our knowledge regarding the factors triggering early microglia activation is, however, incomplete. In this study, we used the cuprizone model to investigate the temporal and causal relationship of oligodendrocyte apoptosis and early microglia activation. Genome-wide gene expression studies revealed the induction of distinct chemokines, among them Cxcl10, Ccl2, and Ccl3 in cuprizone-mediated oligodendrocyte apoptosis. Early microglia activation was unchanged in CCL2- and CCL3-deficient knockouts, but was significantly reduced in CXCL10-deficient mice, resulting in an amelioration of cuprizone toxicity at later time points. Subsequent in vitro experiments revealed that recombinant CXCL10 induced migration and a proinflammatory phenotype in cultured microglia, without affecting their phagocytic activity or proliferation. In situ hybridization analyses suggest that Cxcl10 mRNA is mainly expressed by astrocytes, but also oligodendrocytes, in short-term cuprizone-exposed mice. Our results show that CXCL10 actively participates in the initiation of microglial activation. These findings have implications for the role of CXCL10 as an important mediator during the initiation of neuroinflammatory processes associated with oligodendrocyte pathology.

Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space.

Inflammation is a key process in various diseases, characterized by leukocyte recruitment to the inflammatory site. This study investigates the role of a disintegrin and a metalloproteinase (ADAM) 10 and ADAM17 for leukocyte migration in vitro and in a murine model of acute pulmonary inflammation. Inhibition experiments or RNA knockdown indicated that monocytic THP-1 cells and primary human neutrophils require ADAM10 but not ADAM17 for efficient chemokine-induced cell migration. Signaling and adhesion events that are linked to cell migration such as p38 and ρ GTPase-family activation, F-actin polymerization, adhesion to fibronectin, and up-regulation of α5 integrin were also dependent on ADAM10 but not ADAM17. This was confirmed with leukocytes isolated from mice lacking either ADAM10 or ADAM17 in all hematopoietic cells (vav 1 guanine nucleotide exchange factor [Vav]-Adam10(-/-) or Vav-Adam17(-/-) mice). In lipopolysaccharide-induced acute pulmonary inflammation, alveolar recruitment of neutrophils and monocytes was transiently increased in Vav-Adam17(-/-) but steadily reduced in Vav-Adam10(-/-) mice. This deficit in alveolar leukocyte recruitment was also observed in LysM-Adam10(-/-) mice lacking ADAM10 in myeloid cells and correlated with protection against edema formation. Thus, with regard to leukocyte migration, leukocyte-expressed ADAM10 but not ADAM17 displays proinflammatory activities and may therefore serve as a target to limit inflammatory cell recruitment.

Terminal Ileitis as the Exclusive Manifestation of COVID-19 in Children.

The clinical presentation, organ involvement, and severity of disease caused by SARS-CoV-2 are highly variable, ranging from asymptomatic or mild infection to respiratory or multi-organ failure and, in children and young adults, the life-threatening multisystemic inflammatory disease (MIS-C). SARS-CoV-2 enters cells via the angiotensin-converting enzyme-2 receptor (ACE-2), which is expressed on the cell surfaces of all organ systems, including the gastrointestinal tract. GI manifestations have a high prevalence in children with COVID-19. However, isolated terminal ileitis without other manifestations of COVID-19 is rare. In March 2023, two previously healthy boys (aged 16 months and 9 years) without respiratory symptoms presented with fever and diarrhea, elevated C-reactive protein levels, and low procalcitonin levels. Imaging studies revealed marked terminal ileitis in both cases. SARS-CoV-2 (Omicron XBB.1.9 and XBB.1.5 variants) was detected by nucleic acid amplification in throat and stool samples. Both patients recovered fast with supportive measures only. A differential diagnosis of acute abdominal pain includes enterocolitis, mesenteric lymphadenitis, appendicitis, and more. During SARS-CoV-2 epidemics, this virus alone may be responsible for inflammation of the terminal ileum, as demonstrated. Coinfection with Campylobacter jejuni in one of our patients demonstrates the importance of a complete microbiological workup.

Retrospective identification of the first cord blood-transplanted severe aplastic anemia in a STAT1-associated chronic mucocutaneous candidiasis family: case report, review of literature and pathophysiologic background.

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome whose development can be triggered by environmental, autoimmune, and/or genetic factors. The latter comprises germ line pathogenic variants in genes that bring about habitually predisposing syndromes as well as immune deficiencies that do so only occasionally. One of these disorders is the autosomal dominant form of chronic mucocutaneous candidiasis (CMC), which is defined by germ line STAT1 gain-of-function (GOF) pathogenic variants. The resultant overexpression and constitutive activation of STAT1 dysregulate the Janus kinase/signal transducer and activator of transcription 1 (STAT) signaling pathway, which normally organizes the development and proper interaction of different components of the immunologic and hematopoietic system. Although SAA is an extremely rare complication in this disorder, it gained a more widespread interest when it became clear that the underlying causative pathomechanism may, in a similar fashion, also be instrumental in at least some of the idiopathic SAA cases. Based on these premises, we present herein what is the historically most likely first cord blood-transplanted SAA case in a CMC family with a documented STAT1 GOF pathogenic variant. In addition, we recapitulate the characteristics of the six CMC SAA cases that have been reported so far and discuss the significance of STAT1 GOF pathogenic variants and other STAT1 signaling derangements in the context of these specific types of bone marrow failure syndromes. Because a constitutively activated STAT1 signaling, be it driven by STAT1 GOF germ line pathogenic variants or any other pathogenic variant-independent events, is apparently important for initiating and maintaining the SAA disease process, we propose to acknowledge that SAA is one of the definite disease manifestations in STAT1-mutated CMC cases. For the same reason, we deem it necessary to also incorporate molecular and functional analyses of STAT1 into the diagnostic work-up of SAA cases.

Case report: metoclopramide induced acute dystonic reaction in adolescent CYP2D6 poor metabolizers.

Metoclopramide is indicated for the management of gastroesophageal reflux, gastric stasis, nausea, and vomiting. Metoclopramide-induced acute dystonic reactions (MIADRs), along with repetitive involuntary protrusion of the tongue, are well-known phenomena in children and young adults that may appear after the first dose. The drug is primarily metabolized via oxidation by the cytochrome P450 enzyme CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. A recommendation to decrease metoclopramide dosing in patients with severely limited to no CYP2D6 activity (i.e., poor metabolizers, PMs) is included in the drug label. It is important to note, however, that a requirement or recommendation for pre-emptive testing for CYP2D6 metabolizer status is not included in the drug label. We present two cases of acute dystonia in two non-consanguineous male adolescents: one following metoclopramide and cimetidine administration in a 14-year-old to treat gastroesophageal reflux, and another following metoclopramide and pantoprazole administration in a 17-year-old with acute gastroenteritis. A retrospective pharmacogenetic analysis revealed both patients as CYP2D6 PMs.

Elevated lipopolysaccharide in the colon evokes intestinal inflammation, aggravated in immune modulator-impaired mice.

Frequency of gram-negative bacteria is markedly enhanced in inflamed gut, leading to augmented LPS in the intestine. Although LPS in the intestine is considered harmless and, rather, provides protective effects against epithelial injury, it has been suggested that LPS causes intestinal inflammation, such as necrotizing enterocolitis. Therefore, direct effects of LPS in the intestine remain to be studied. In this study, we examine the effect of LPS in the colon of mice instilled with LPS by rectal enema. We found that augmented LPS on the luminal side of the colon elicited inflammation in the small intestine remotely, not in the colon; this inflammation was characterized by body weight loss, increased fluid secretion, enhanced inflammatory cytokine production, and epithelial damage. In contrast to the inflamed small intestine induced by colonic LPS, the colonic epithelium did not exhibit histological tissue damage or inflammatory lesions, although intracolonic LPS treatment elicited inflammatory cytokine gene expression in the colon tissues. Moreover, we found that intracolonic LPS treatment substantially decreased the frequency of immune-suppressive regulatory T cells (CD4(+)/CD25(+) and CD4(+)/Foxp3(+)). We were intrigued to find that LPS-promoted intestinal inflammation is exacerbated in immune modulator-impaired IL-10(-/-) and Rag-1(-/-) mice. In conclusion, our results provide evidence that elevated LPS in the colon is able to cause intestinal inflammation and, therefore, suggest a physiological explanation for the importance of maintaining the balance between gram-negative and gram-positive bacteria in the intestine to maintain homeostasis in the gut.

Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that mainly affects cattle. Transmission of BSE to humans caused a variant form of Creutzfeldt-Jakob disease. Following infection, the protease-resistant, disease-associated isoform of prion protein (PrP(Sc)) accumulates in the central nervous system and in other tissues. Many countries have defined bovine tissues that may contain prions as specified risk materials, which must not enter the human or animal food chains and therefore must be discarded. Ultrasensitive techniques such as protein misfolding cyclic amplification (PMCA) have been developed to detect PrP(Sc) when present in minuscule amounts that are not readily detected by other diagnostic methods such as immunohistochemistry or Western blotting. This study was conducted to determine when and where PrP(Sc) can be found by PMCA in cattle orally challenged with BSE. A total of 48 different tissue samples from four cattle infected orally with BSE at various clinical stages of disease were examined using a standardized PMCA protocol. The protocol used brain homogenate from bovine PrP transgenic mice (Tgbov XV) as substrate and three consecutive rounds of PMCA. Using this protocol, PrP(Sc) was found in the brain, spinal cord, nerve ganglia, optic nerve and Peyer's patches. The presence of PrP(Sc) was confirmed in adrenal glands, as well as in mesenteric lymph nodes - a finding that was reported recently by another group. Interestingly, additional positive results were obtained for the first time in the oesophagus, abomasum, rumen and rectum of clinically affected cattle.

Rehospitalization in the first 2 years of life in children born preterm.

AIM: Aim of the study is to investigate the frequency of and predictors for rehospitalization within the first 2 years of life among preterm infants. METHODS: All children born before 32 weeks of gestation in Northern Tyrol between January 2003 and July 2008 were prospectively enrolled. Data on rehospitalizations were obtained from hospital admission records. The association between candidate risk factors and readmission was analysed by means of logistic regression analysis. RESULTS: In the first and second years of life, 151 and 93 of 377 children (40.1% and 24.7%), respectively, were readmitted to one of the hospitals in Northern Tyrol. The most common causes of rehospitalization were respiratory disorders, accounting for 42.1% and 47.4% of total readmissions in the first and second years of life. Chronic lung disease (CLD), male sex and smoking in pregnancy were risk conditions relevant to readmission in the first year of life, but only CLD in the second year. CONCLUSION: Infants born before 32 weeks of gestation have a high risk of rehospitalization with respiratory illness significantly contributing to postdischarge morbidity. Neonatal intensive care should aim to further improve respiratory health in preterm infants, and adequate follow-up services must be offered.

Robotically Assisted Surgery in Children-A Perspective.

The introduction of robotically assisted surgery was a milestone for minimally invasive surgery in the 21st century. Currently, there are two CE-approved robotically assisted surgery systems for use and development in pediatrics. Specifically, tremor filtration and optimal visualization are approaches which can have enormous benefits for procedures in small bodies. Robotically assisted surgery in children might have advantages compared to laparoscopic or open approaches. This review focuses on the research literature regarding robotically assisted surgery that has been published within the past decade. A literature search was conducted to identify studies comparing robotically assisted surgery with laparoscopic and open approaches. While reported applications in urology were the most cited, three other fields (gynecology, general surgery, and "others") were also identified. In total, 36 of the publications reviewed suggested that robotically assisted surgery was a good alternative for pediatric procedures. After several years of experience of this surgery, a strong learning curve was evident in the literature. However, some authors have highlighted limitations, such as high cost and a limited spectrum of small-sized instruments. The recent introduction of reusable 3 mm instruments to the market might help to overcome these limitations. In the future, it can be anticipated that there will be a broader range of applications for robotically assisted surgery in selected pediatric surgeries, especially as surgical skills continue to improve and further system innovations emerge.

Influence of different modeling strategies for the periodontal ligament on finite element simulation results.

INTRODUCTION: The finite element method is a promising tool to investigate the material properties and the structural response of the periodontal ligament (PDL). To obtain realistic and reproducible results during finite element simulations of the PDL, suitable bio-fidelic finite element meshes of the geometry are essential. METHODS: In this study, 4 independent coworkers generated altogether 17 volume meshes (3-dimensional) based on the same high-resolution computed-tomography image data set of a tooth obtained in vivo to compare the influence of the different model generation techniques on the predicted response to loading for low orthodontic forces. RESULTS: It was shown that the thickness of the PDL has a significant effect on initial tooth mobility but only a remarkably moderate effect on the observed stress distribution in the PDL. Both the tooth and the bone can be considered effectively rigid when exploring the response of the PDL under low loads. The effect of geometric nonlinearities could be neglected for the applied force system. CONCLUSIONS: Most importantly, this study highlights the sensitivity of the finite element simulation results for accurate geometric reconstruction of the PDL.

Controlled growth of ordered monolayers of N-heterocyclic carbenes on silicon.

N-Heterocyclic carbenes (NHCs) are promising modifiers and anchors for surface functionalization and offer some advantages over thiol-based systems. Because of their strong binding affinity and high electron donation, NHCs can dramatically change the properties of the surfaces to which they are bonded. Highly ordered NHC monolayers have so far been limited to metal surfaces. Silicon, however, remains the element of choice in semiconductor devices and its modification is therefore of utmost importance for electronic industries. Here, a comprehensive study on the adsorption of NHCs on silicon is presented. We find covalently bound NHC molecules in an upright adsorption geometry and demonstrate the formation of highly ordered monolayers exhibiting good thermal stability and strong work function reductions. The structure and ordering of the monolayers is controlled by the substrate geometry and reactivity and in particular by the NHC side groups. These findings pave the way towards a tailor-made organic functionalization of silicon surfaces and, thanks to the high modularity of NHCs, new electronic and optoelectronic applications.

Combination of Ceramic Laser Micromachining and Printed Technology as a Way for Rapid Prototyping Semiconductor Gas Sensors.

The work describes a fast and flexible micro/nano fabrication and manufacturing method for ceramic Micro-electromechanical systems (MEMS)sensors. Rapid prototyping techniques are demonstrated for metal oxide sensor fabrication in the form of a complete MEMS device, which could be used as a compact miniaturized surface mount devices package. Ceramic MEMS were fabricated by the laser micromilling of already pre-sintered monolithic materials. It has been demonstrated that it is possible to deposit metallization and sensor films by thick-film and thin-film methods on the manufactured ceramic product. The results of functional tests of such manufactured sensors are presented, demonstrating their full suitability for gas sensing application and indicating that the obtained parameters are at a level comparable to those of industrial produced sensors. Results of design and optimization principles of applied methods for micro- and nanosystems are discussed with regard to future, wider application in semiconductor gas sensors prototyping.

Long-term outcome of initially homogenously treated and relapsed childhood acute lymphoblastic leukaemia in Austria--a population-based report of the Austrian Berlin-Frankfurt-Münster (BFM) Study Group.

Relapsed acute lymphoblastic leukaemia (ALL) is the most common cause for a fatal outcome in paediatric oncology. Although initial ALL cure rates have improved up to 80%, the prognosis of recurrent ALL remains dismal with event-free-survival (EFS) rates about 35%. In order to analyse a population-based cohort with uniform treatment of initial disease, we examined the outcome of children suffering from relapsed ALL in Austria for the past 20 years and the validity of the currently used prognostic factors (e.g. time to and site of relapse, immunophenotype). Furthermore, we compared survival rates after chemotherapy alone with those after allogeneic stem cell transplantation (SCT). All 896 patients who suffered from ALL in Austria between 1981 and 1999 were registered in a prospectively designed database and treated according to trials ALL-Berlin-Frankfurt-Münster (BFM)-Austria (A) 81, ALL-A 84 and ALL-BFM-A 86, 90 and 95. Of these, 203 (23%) suffered from recurrent disease. One-hundred-and-seventy-two patients (85%) achieved second complete remission. The probability of 10-year EFS for the total group was 34 +/- 3%. Clinical prognostic markers that independently influenced survival were time to relapse, site of relapse and the immunophenotype. Additionally, a Cox regression model demonstrated that allogeneic SCT after first relapse was associated with a superior EFS compared with chemo/radiotherapy only (hazard ratio = 0.254; P = 0.0017).

Annealing of Gadolinium-Doped Ceria (GDC) Films Produced by the Aerosol Deposition Method.

Solid oxide fuel cells need a diffusion barrier layer to protect the zirconia-based electrolyte if a cobalt-containing cathode material like lanthanum strontium cobalt ferrite (LSCF) is used. This protective layer must prevent the direct contact and interdiffusion of both components while still retaining the oxygen ion transport. Gadolinium-doped ceria (GDC) meets these requirements. However, for a favorable cell performance, oxide ion conducting films that are thin yet dense are required. Films with a thickness in the sub-micrometer to micrometer range were produced by the dry room temperature spray-coating technique, aerosol deposition. Since commercially available GDC powders are usually optimized for the sintering of screen printed films or pressed bulk samples, their particle morphology is nanocrystalline with a high surface area that is not suitable for aerosol deposition. Therefore, different thermal and mechanical powder pretreatment procedures were investigated and linked to the morphology and integrity of the sprayed films. Only if a suitable pretreatment was conducted, dense and well-adhering GDC films were deposited. Otherwise, low-strength films were formed. The ionic conductivity of the resulting dense films was characterized by impedance spectroscopy between 300 °C and 1000 °C upon heating and cooling. A mild annealing occurred up to 900 °C during first heating that slightly increased the electric conductivity of GDC films formed by aerosol deposition.