The 10 most recently published documents
Background & Aim:
In an aging society, promoting successful cognitive aging is becoming increasingly important, particularly with regard to age-related cognitive changes and dementia. Therefore, it is critical to support older people, especially those with subjective cognitive decline, through helpful tools and identify effective interventions to alleviate dementia symptoms. While pharmacological treatments have their limitations, such as limited efficacy and side effects, non-pharmacological interventions are becoming increasingly important. The aim of this dissertation was to evaluate non-pharmacological interventions, specifically coping strategies at the beginning of the cognitive spectrum and later non-pharmacological interventions in gen-eral for the treatment of dementia symptoms, in the German healthcare system.
Methods:
First, effective coping strategies were identified by systematically reviewing scientific evidence and then the strategies were included in a memory aid handbook for people with subjective cognitive decline. The memory aid handbook was tested and evaluated in a usability study to determine whether its use had positive effects on people with subjective cognitive decline. Moreover, the implementation of non-pharmacological interventions in German de-mentia care, as well as perceived effects and barriers were examined through focus group discussions with caregivers in general and specifically in interviews with informal caregivers.
Results:
Findings from the systematic review indicated that coping strategies are used across the spectrum of cognitive decline, although the nature of these strategies varied with the severity of impairment. The memory aid handbook, developed based on effective coping strate-gies, has proven to be a useful tool for supporting people with subjective cognitive decline. Participants were able to integrate new strategies and increase their confidence in their already established coping strategies. Further, findings from interviews and expert focus group discussions indicated that other non-pharmacological interventions, particularly social interactions and interventions tailored to the person with dementia, are used to alleviate dementia symptoms and improve the well-being of people with dementia and their caregivers. Despite the perceived positive effects, barriers such as bureaucracy, lack of staff and resources, lack of time, and limited services hindered implementation of non-pharmacological interventions.
Conclusion:
Non-pharmacological interventions are perceived as beneficial by people with subjective cognitive decline and in dementia, although the type of intervention preferred varies. By incorporating a person-centered care approach, non-pharmacological interventions might reach their full potential, although their implementation is hindered by several barriers that need to be addressed in future model projects within the community.
Peatland rewetting is a recognized nature-based solution to reduce CO2 emissions and has the potential to create carbon sinks. The necessity to reduce greenhouse gases (GHG) from both natural and from anthropogenic sources is one of the most urgent challenges of our time. Rewetting artificially drained peatlands with freshwater can induce initially high methane (CH4) emissions. Using sulfate-containing brackish water to rewet coastal peatlands may prevent these CH4 peaks. This is due to substrate usage by thermodynamically more favorable microbial metabolic processes, such as sulfate reduction, instead of methanogenesis. Together with colleagues, I investigated two peatlands with different histories of rewetting and management, located on the Baltic Sea coast in north-east Germany: A coastal fen that was rewetted with freshwater and another rewetted with brackish water. In the freshwater rewetted fen, which experienced a drought shortly before a storm surge inundated the area with brackish water, a reduction of its previously high CH4 emissions was observed. While abundances of methanogenic archaea decreased during the drought, we did not see a further reduction after the brackish water inflow. Although a large part of the CH4 emission reduction is certainly a legacy effect of the drought, the increasing abundances of sulfate-reducing bacteria (SRB) following the inflow may have caused competition with methanogens for substrate. In addition or alternatively, SRB might be involved in the anaerobic oxidation of CH4. However, we did not observe increases in CH4 oxidation or in abundances of anaerobic methanotrophs in the peat soil. This suggests that methanotrophy may have taken place in the water column above the investigated peat soil. In contrast, the brackish water rewetted fen showed relatively low CH4 emissions immediately after rewetting compared to freshwater rewetted fens. Relative to the fen’s drained state, abundances of SRB and methanogens increased after rewetting, but substrate competition and CH4 oxidation most likely limited excess CH4 emissions. However, the high CO2 emissions did not decrease as expected despite rewetting, while ecosystem respiration and thus peat decomposition was significantly reduced. We observed a severe die-back of both grassland plants and near-ditch fen vegetation following the intense inundation with brackish water. The reason for the persistent CO2 emissions after rewetting could be ecosystem respiration, which was fueled by large amounts of available labile substrate, irrespectively of peat decay. Additionally, high CO2 emissions could not be prevented due to the lack of CO2 uptake by photosynthesis. This thesis contributes to the discussion on coastal peatland rewetting and provides new ideas about the interplay between a fen’s microbiology and biogeochemistry among different spatial compartments. When aiming for GHG emission reduction after rewetting this thesis highlights that not only the water type might be important to consider, but also the frequency of brackish water input as well as the flooding intensity. In order to define and evaluate rewetting approaches for future projects, comparing rewetted peatlands according to their GHG emission development is necessary. Further, long-term monitoring and multidisciplinary research are needed to provide insight on the influence of brackish water on coastal fens beyond the first year after rewetting.
Das Ziel der vorliegenden Dissertation war die Erörterung der Frage „Wie ist die Durchführbarkeit einer telemedizinischen Behandlung von Patienten einer psychiatrischen Institutsambulanz und einer Tagesklinik eines Universitätsklinikums in Deutschland, um die Kontinuität der Versorgung während des ersten COVID-19 Lockdowns zu gewährleisten und wie zufrieden sind die Patienten und Therapeuten?“. Es wurden die Daten einer Beobachtungsstudie während des ersten COVID-19 Lockdowns ausgewertet, in der Patienten in laufender oder neu begonnener ambulanter psychiatrischer Therapie sowie Patienten, die vorzeitig aus der Tagesklinik entlassen werden mussten, telemedizinisch behandelt wurden.
Über die Hälfte der Patienten und Therapeuten gaben an, dass die Besprechung von Problemen und Bedürfnissen über das Telefon genauso gut funktionierte wie in den persönlichen Konsultationen. In der Untergruppe der Patienten, die aufgrund einer vorzeitigen Entlassung aus der Ta-gesklinik neu zur Therapie kamen, war die Akzeptanz sogar noch höher und die Telemedizin wurde in 87,5 % der Kontakte als gleich gut bewertet.
Sowohl Patienten als auch Therapeuten waren der Meinung, dass die telemedizinische Betreu-ung während des Lockdowns eine Alternative zur üblichen Therapie in der Ambulanz darstellt und dass die Möglichkeit der telemedizinischen Betreuung für die Dauer der Coronavirus-Pandemie beibehalten werden sollte.
Die Ergebnisse zeigen einen klaren Trend zur Zufriedenheit mit und Akzeptanz von telemedizinischer Betreuung in einer heterogenen Gruppe von nicht vorselektierten psychiatrischen Patienten. Obwohl die Zahl der Patienten gering ist, deuten die Ergebnisse darauf hin, dass die überwiegend positiven Ergebnisse von telemedizinischen Konzepten in Forschungsprojekten wahrscheinlich auf reale Versorgungssituationen übertragen werden können.
Telemedizin kann, wenn es die Umstände erforderlich machen, wie zum Beispiel in einer Pan-demiesituation, eine effektive Alternative in der psychiatrischen Patientenversorgung bieten, um die kontinuierliche Betreuung zu gewährleisten.
Darüber hinaus stellt die Telemedizin auch außerhalb der Pandemiesituation eine potentielle Erweiterung der Therapie von Patienten in der ambulanten psychiatrischen Versorgung dar.
Vor allem diese hybride Versorgung kann auch auf andere Fachgebiete erweitert werden. Damit könnten nicht nur Engpässe, sondern zum Beispiel auch eine eingeschränkte Mobilität der Pati-enten abgemildert werden.
Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia
(2023)
Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.
Background
Paediatric inflammatory bowel disease (PIBD) patients require chronic care over the lifespan. Care for these patients is complex, as it is adapted for childrens’ life stages and changing disease activity. Guideline based care for this patient group recommends a multidisciplinary approach, which includes in addition to paediatric gastroenterologists, nutritional and psychological care services. For PIBD patients, a discrepancy between available guideline-based multidisciplinary care and actual care has been found from the provider side, but to what extent patients experience this is unclear.
Objectives
To identify which healthcare services were used and whether socio-demographic, geographic or disease related factors have an influence on health service utilisation.
Methods
A standardised questionnaire (CEDNA) was distributed amongst parents of children aged 0–17 diagnosed with PIBD and adolescents (aged 12–17) with a PIBD. Items related to health service use were analysed, these included specialist care, additional care services, reachability of services and satisfaction with care. Logistic regression models on additional service use were calculated. Service availability and reachability maps were made.
Results
Data was analysed for 583 parent and 359 adolescent questionnaires. Over half of the respondents had Crohn’s Disease (CD, patients n = 186 parents n = 297). Most patients and parents reported their paediatric gastroenterologist as their main care contact (patients 90.5%; parents 93%). Frequently reported additional services were nutritional counselling (patients 48.6%; parents 42.2%) and psychological support (patients 28.1%; parents 25.1%). Nutritional counselling was more frequently reported by CD patients in both the patient (OR 2.86; 95%CI 1.73–4.70) and parent (OR 3.1; 95%CI 1.42–6.71) sample. Of the patients, 32% reported not using any additional services, which was more likely for patients with an illness duration of less than one year (OR 3.42; 95%CI 1.26–9.24). This was also observed for the parent population (OR 2.23; 95%CI 1.13–4.4). The population-based density of specialised paediatric gastroenterologists was not proportionate to the spatial distribution of patients in Germany, which may have an influence on access.
Conclusions
Parents and children reported highly specialised medical care. Multidisciplinary care offers do not reach the entire patient population. Access to multidisciplinary services needs to be ensured for all affected children.
Die vorliegende Arbeit ist als eine Pilotstudie zur Untersuchung der Anwendbarkeit eines KI-basierten Vaskulären Schweregradscores (VSS) im Screening der Frühgeborenenretinopathie zu verstehen. Dazu ist ein großer Bilddatensatz aus der randomisierten, prospektiven CARE-ROP-Studie (48) mit dem computergestützten i-ROP-Algorithmus ausgewertet und anschließend mit den klinischen Angaben zum Krankheitsverlauf in Relation gesetzt worden.
Die Ergebnisse dieser Arbeit belegen, dass der VSS sowohl für das primäre (vor einer Anti-VEGF-Therapie) als auch für das sekundäre ROP-Screening (nach einer Anti-VEGF-Therapie zur Überwachung einer Reaktivierung) von Nutzen sein kann. Demnach korreliert der VSS mit der klinisch beobachteten Krankheitsregression nach initialer Ranibizumab-Injektion sowie mit der anschließenden Krankheitsprogression im Falle einer behandlungsbedürftigen Reaktivierung. Darüber hinaus ist das Ausmaß der VSS-Änderungsrate (Δ) zwischen Baseline-Visite und Woche 1 mit einer höheren Wahrscheinlichkeit für eine spätere behandlungsbedürftige Reaktivierung sowie die Höhe des VSS zu Therapiebeginn mit einem früheren Zeitpunkt der ersten Wiederbehandlung assoziiert (78). Zudem wird deutlich, dass die Schweregradbestimmung der Plus Disease trotz bestehender Klassifikationskriterien aufgrund der subjektiven Interpretation von pathologischen Grenzwerten für vaskuläre Veränderungen auch für Expert*innen herausfordernd sein kann (64–66). Hier können KI-basierte Systeme im Vergleich zur menschlichen Befundung möglicherweise mehr Objektivität bieten und damit die Qualität sowie Zuverlässigkeit des ROP-Screenings erhöhen. Zusätzlich besteht bei einer klinischen Anwendung die Möglichkeit, durch eine telemedizinische Beurteilung von Fundusbildern die Erreichbarkeit des Screenings auch in medizinisch unterversorgten Regionen zu verbessern (73,84).
Letztlich muss jedoch berücksichtigt werden, dass mit den vorliegenden Ergebnissen aufgrund der angeführten Limitationen nur Hypothesen formuliert werden können, deren Validierung Gegenstand künftiger prospektiver Studien sein sollte. Wenn es sich bestätigt, dass bereits zu Beginn der Behandlung Kinder mit einem erhöhten Wiederbehandlungsrisiko herausgefiltert und anhand der Höhe des VSS-Ausgangswertes auch der ungefähre Zeitpunkt einer Reaktivierung abgeschätzt werden kann, hätte dies bedeutsame Auswirkungen auf die Planung von Verlaufskontrollen nach einer Anti-VEGF-Therapie. Damit würde die Qualität und Sicherheit der ROP-Behandlung entscheidend verbessert werden können.
Insects have a long evolutionary history, as they have existed at least since Carboniferous (ca. 360 mya or million years ago) and potentially even since the Devonian (ca. 410 mya). Today they can be found in almost every habitat on earth and have thusly a very wide array of ecological strategies. To better understand their ecological strategies, especially predatory and defensive strategies, and their evolutionary history, it is crucial to also study fossil insects, as they can give a unique insight into the types of ecological strategies that were present in the past, some of which may still be found exhibited by insects today, but some of which are not. There are four approaches which are especially relevant in studying predatory and defensive strategies of insects in the fossil record: 1) specialised morphology, 2) phylogenetic position, 3) trace fossils and 4) group fossilisation and ‘frozen behaviour’.
Specialised morphology pertaining to a predatory lifestyle, especially in insects (but also arthropods as a whole), usually involves raptorial appendages, with which they can grasp their prey, and/or additionally venom injecting structures. In animals employing a defensive strategy, their morphology may be specialised in either aiding them in escaping their predator, e.g. with jumping, or in actively or passively defending against their predators, e.g. with defensive hairs. Their are also specialised morphologies that aid both predators and defensive insects, especially ones pertaining to camouflage and mimicry, as these strategies aim to send a false signal to either their predator or prey to not be recognized and/or detected by them and thus either more easily escape their predators (in the case of defensive insects) or catch their prey more easily (in the case of predators).
The phylogenetic position of a fossil insect can help in combination with a comparison with extant representatives of the group it belongs within to point out general trends in their lifestyles. But this approach is best used in combination with the other approaches.
Trace fossils, and related phenomena, that pertain to predatory and defensive life strategies, are traces of injuries (e.g. potential predation events), coprolites (fossilised excrements) and fossilised re-gurgitate (“Speiballen”) (both of which can contain prey items and a producer, i.e. the predator, may potentially be ascertained) and fossilised stomach content (where usually both the predator and the prey item is preserved).
Group fossilisations are fossils that contain groups of organisms, and can also be a predator and its prey (where its either a group of prey organisms, or also predators). Frozen behaviour are fossils where the organism is fossilised while exhibiting any type of behaviour (‘frozen in time’). This can be one organism, but also the interaction of two or more organisms, and in this later case this may also pertain to a predator-prey interaction thusly ‘caught’ and fossilised.
In this thesis the above mentioned approaches in studying predatory and defensive strategies of insects in the fossil record are discussed in the context of various insect in-groups, as exemplary cases illustrating different aspects of one or more of these approaches, and the applicability and limitations of these approaches are critically discussed.
Background
At-risk alcohol use and tobacco smoking often co-occur. We investigated whether brief alcohol interventions (BAIs) among general hospital patients with at-risk alcohol use may also reduce tobacco smoking over 2 years. We also investigated whether such effects vary by delivery mode; i.e. in-person versus computer-based BAI.
Methods
A proactively recruited sample of 961 general hospital patients with at-risk alcohol use aged 18 to 64 years was allocated to three BAI study groups: in-person BAI, computer-based BAI, and assessment only. In-person- and computer-based BAI included motivation-enhancing intervention contacts to reduce alcohol use at baseline and 1 and 3 months later. Follow-ups were conducted after 6, 12, 18 and 24 months. A two-part latent growth model, with self-reported smoking status (current smoking: yes/no) and number of cigarettes in smoking participants as outcomes, was estimated.
Results
Smoking participants in computer-based BAI smoked fewer cigarettes per day than those assigned to assessment only at month 6 (meannet change = − 0.02; 95% confidence interval = − 0.08–0.00). After 2 years, neither in-person- nor computer-based BAI significantly changed smoking status or number of cigarettes per day in comparison to assessment only or to each other (ps ≥ 0.23).
Conclusions
While computer-based BAI also resulted in short-term reductions of number of cigarettes in smoking participants, none of the two BAIs were sufficient to evoke spill-over effects on tobacco smoking over 2 years. For long-term smoking cessation effects, multibehavioural interventions simultaneously targeting tobacco smoking along with at-risk alcohol use may be more effective.
Trial registration number: NCT01291693.
Background
Cross-border cooperation of emergency medical services, institutions and hospitals helps to reduce negative impact of national borders and consecutive discrimination of persons living and working in border regions. This study aims to explore the feasibility and effectiveness of a cross-border bilingual simulation training for emergency medical services within an INTERREG-VA-funded project.
Methods
Five days of simulation training for German and Polish paramedics in mixed groups were planned. Effectiveness of training and main learning objectives were evaluated as pre-post-comparisons and self-assessment by participants.
Results
Due to COVID-19 pandemic, only three of nine training modules with n = 16 participants could be realised. Cross-border-simulation training was ranked more positively and was perceived as more useful after the training compared to pretraining. Primary survey has been performed using ABCDE scheme in 18 of 21 scenarios, whereas schemes to obtain medical history have been applied incompletely. However, participants stated to be able to communicate with patients and relatives in 10 of 21 scenarios.
Conclusion
This study demonstrates feasibility of a bilingual cross-border simulation training for German and Polish rescue teams. Further research is highly needed to evaluate communication processes and intra-team interaction during bilingual simulation training and in cross-border emergency medical services rescue operations.
Background
Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen.
Methods
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients’ global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed.
Discussion
This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care.
Trial registration
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680