Влияние палеоклимата на геотермический режим и нефтегенерационный потенциал баженовской свиты (на широтах Томской области)

Проведено многовариантное палеотемпературное моделирование осадочных разрезов шести глубоких скважин Томской области. Определено существенное влияние векового хода температур на поверхности Земли (палеоклимат) на термическую историю и реализацию нефтегенерационного потенциала отложениями баженовской свиты для различных тектонических структур, расположенных на разных широтах Томской области. В качестве критериев адекватности модели геотермического режима приняты "реперные" геотемпературы из отражательной способности витринита и нефтегазоносность верхнеюрских отложений

Wall and Vault Construction in Mark Brandenburg During the 18th and early 19th Centuries

In dieser Arbeit sind die Mauer- und Gewölbekonstruktionen Forschungsgegenstand, so wie sie während des 18. und des frühen 19. Jh. entwickelt und in der Mark Brandenburg ausgeführt wurden. Den Schwerpunkt der Arbeit bilden die relevanten Baumaterialien, Herstellungstechniken und Konstruktionen der Mauern und Gewölbe. Dazu werden theoretisch beschriebene Mau-er- und Gewölbekonstruktionen anhand einzelner heute noch in der Mark Brandenburg exi-stierender Gebäude verifiziert. Es wird das konstruktive Verständnis erforscht, welches während des 18. und frühen 19. Jh. der Errichtung von Gebäuden zugrunde lag. Dabei werden prägende kulturelle, wirt-schaftliche und wissenschaftliche Impulse beachtet. Als wesentliche Aspekte werden das historische Verständnis zur Standsicherheit und die darauf abgestimmten Bewertungen ein-zelner Baumaterialien, Verarbeitungstechniken und Konstruktionen untersucht. Es wird das wachsende Bestreben aufgezeigt, um geeignete Kriterien zur besseren Beurteilung der Standsicherheit zu entwickeln. Der Untersuchungsraum ist auf das Territorium der Mark Brandenburg begrenzt, das während des Untersuchungszeitraums kontinuierlich unter kurmärkischer Verwaltung stand. Dies sind das heutige Bundesland Berlin und Teile des Bundeslandes Brandenburg mit den Landkreisen Barnim, Dahme-Spreewald, Frankfurt, Havelland, Märkisch-Oderland, Oberha-vel, Oder-Spree, Ostprignitz-Ruppin, Potsdam, Potsdam-Mittelmark, Prignitz, Teltow-Fläming und Uckermark. Die Erforschung der Mauer- und Gewölbekonstruktionen dient als Grundlage für bauhisto-rische Untersuchungen und soll eine konstruktive Beurteilung zu sanierender oder instandzu-setzender Gebäude erleichtern.The object of this research is to present the developenes and practice of wall and vault construction in Mark Brandenburg during the 18th and early 19th centuries. The main emphasis focuses on the relavent building materials, production techniques as well as the actual construction of walls and vaults. The theoretical desciptions there of are verified on the basic of examples of buildings still excisting in Mark Brandenburg. The research deals with the basic constructional understanding used to erect buildings during the 18th and early 19th centuries. The forming influence of cultural, economic, as well as scientific impulses are observed. Essential aspects are the examination of historical understanding of architectual stability and the requisite evaluation of individual building materials, workmanship techniques and construction designs. The ever increasing ambition to set appropriate standards in order to develope a better judgement of constructional stability is demonstrated. The area to be examined is limited to the terretory of Mark Brandenburg which during the previously mentioned timespan was under the jusistiction of the Kurmark administration. Specifically this consists of the present-day state of Berlin, and the parts of the state of Brandenburg which include the counties of Barnim, Dahme-Spreewald, Frankfurt, Havelland, Märkisch-Oderland, Oberhavel, Oder-Spree, Ostprignitz-Ruppin, Potsdam, Potsdam-Mittelmark, Prignitz, Teltow-Fläming and Uckermark. The study of wall and vault construction serves as a basis for the examination of historic building practice and provides a constructional analysis designed to facilitate the evaluation of reconstruction or renovation plans pertaining to such buildings

Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity

Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The results showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery : the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA)

Non-cardiac surgery; Pre-operative cardiac risk assessment; Pre-operative cardiac testing; Pre-operative coronary artery revascularization; Perioperative cardiac management; Renal disease; Pulmonary disease; Neurological disease; Anaesthesiology; Post-operative cardiac surveillanc

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland

<p>Abstract</p> <p>Background</p> <p>Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic.</p> <p>Methods</p> <p>Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods.</p> <p>Results</p> <p>7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis.</p> <p>Conclusion</p> <p>Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.</p

Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 study

SIMPLE SUMMARY: A medulloblastoma recurrence is usually associated with an unfavorable prognosis. The German P-HIT-REZ 2005 Study gathered data from patients with relapsed medulloblastomas treated in different, non-randomized therapy arms dependent on preconditions of the patients (previous treatment, comorbidities, relapse pattern), the decision of treating physicians, and the patients’/parents’ choice. A total of 93 evaluable patients with refractory or relapsed medulloblastoma were enrolled. The main aim of this study was to analyze the impact of patient and disease characteristics as well as local and systemic therapies on post-relapse progression-free (PFS) and overall survival (OS). In multivariate analysis, a short time until the first recurrence (<18 months) was the strongest predictor for a worse PFS and OS, which was mainly associated with molecular subgroup 3. Metastatic disease, at relapse, only had a significant impact on OS. Re-biopsy, at relapse, is highly recommended to investigate the histopathological and molecular genetic tumor characteristics and to exclude a secondary malignancy. ABSTRACT: Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9–16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7–10.0) and 18.5 months (CI: 13.6–23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients’ survival

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis

We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years

Medical Honey for Wound Care—Still the ‘Latest Resort’?

While the ancient Egyptians and Greeks used honey for wound care, and a broad spectrum of wounds are treated all over the world with natural unprocessed honeys from different sources, Medihoney™ has been one of the first medically certified honeys licensed as a medical product for professional wound care in Europe and Australia. Our experience with medical honey in wound care refers only to this product. In this review, we put our clinical experience into a broader perspective to comment on the use of medical honey in wound care. More prospective randomized studies on a wider range of types of wounds are needed to confirm the safety and efficacy of medical honey in wound care. Nonetheless, the current evidence confirming the antibacterial properties and additional beneficial effects of medical honey on wound healing should encourage other wound care professionals to use CE-certified honey dressings with standardized antibacterial activity, such as Medihoney™ products, as an alternative treatment approach in wounds of different natures

Time trends in mechanical thrombectomy (2017–2021): do real-world data reflect advances in evidence?

Background: In recent years, we have witnessed a continuous, evidence-based expansion of indications for endovascular therapy (EVT) in the treatment of ischaemic stroke, driven by advancements in extended time windows and target vessel occlusion. Our study aimed to evaluate the temporal changes in patients’ characteristics, treatment, and outcomes in clinical practice. Methods: We used data from the German Stroke Registry, a large national multicentre prospective registry, which includes all patients receiving EVT for ischaemic stroke at its participating centers. We analysed baseline factors, treatment details, and clinical outcomes [Modified Rankin Scale (mRS) at 3 months] over a 5-year period (2017–2021). Results: We included 6,251 patients from eight centres. Over time, the characteristics of patients undergoing EVT changed in several aspects (2017 vs. 2021). Patients became older (median age from 76 [IQR: 65–82] to 77 [65–84 years]; ptrend = 0.02), and less severely affected (NIHSS from 15 [11–19] to 13 [8–18]; ptrend <0.001). There was an increase in patients treated more than 6 h after last seen well (22.0% to 28.3%; ptrend<0.001), and more patients were treated for medium vessel occlusion (16.1% to 28.1%; ptrend<0.001). The use of intravenous thrombolysis decreased (52.4% to 40.4%; ptrend<0.01). Good functional outcome declined (percentage of patients with mRS ≤ 2 from 36.0 to 34.9%; aOR 0.94 per year [0.89–0.99]), while mortality at 3 months increased from 25.3% in 2017 to 34.7% in 2021; aOR 1.13 per year [1.07–1.19]. Conclusion: Between 2017 and 2021, there were significant shifts in the demographic and clinical profiles of patients undergoing EVT, along with an expansion in EVT indications. Despite these patients presenting with less severe stroke symptoms, improvements in functional outcomes were not observed, and mortality rates increased. These trends may reflect willingness to treat patients with more severe underlying health conditions

The human milk oligosaccharide 3′sialyllactose reduces low-grade inflammation and atherosclerosis development in mice

Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3'SL attenuates mRNA levels of a selected set of inflammatory genes and promotes the activity of liver X receptor (LXR) and sterol regulatory element binding protein-1 (SREBP1). These acute antiinflammatory effects of 3'SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CCCTC-binding factor (CTCF), IFN regulatory factor 2 (IRF2), B cell lymphoma 6 (BCL6), and other transcription factor recognition motifs. In a murine atherosclerosis model, both s.c. and oral administration of 3'SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3'SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease