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Assessment einer Neuropathie – mit welchen Messmethoden lässt sie sich abbilden und welche Konsequenzen ziehen wir daraus für die Klinik
No full textHintergrund
Eine mit der Chemotherapie oft einhergehende und äusserst relevante ungewollte Nebenwirkung ist die Chemotherapie-induzierte periphere Polyneuropathie (CIPN). Es besteht die Möglichkeit, dass sie sowohl als unmittelbare Nebenwirkung als auch als langfristige, chronische Folge der Anwendung vieler gängiger Chemotherapeutika auftritt. Bislang gibt es allerdings in der pädiatrischen Onkologie noch keine allgemeingültige Methode zur Diagnosestellung einer CIPN. PrepAir definiert ein Goldstandard-Assessment, um eine CIPN frühzeitig zu erkennen und auch zu behandeln. Die Anwendbarkeit dieses Assessments wurde bereits an gesunden Kindern und Jugendlichen im Alter von sechs bis 18 Jahren erfolgreich geprüft. Dabei wurden relevante und wichtige Referenzwerte hergestellt.
Methoden
Die Studie wird als Querschnittsstudie aufgebaut. Die Stichprobe besteht aus Kinderpatienten, welche innerhalb der nächsten 48-Stunden eine Chemotherapie erhalten. Dabei gibt es eine Baseline-Messung, welche vor Eingriff der Chemotherapie stattfindet, eine Messung nach drei Monaten und eine Messung nach Abschluss der Chemotherapie. Die Patienten werden randomisiert in eine Kontroll- und Interventionsgruppe eingeteilt. Das Assessment beinhaltet den ped-mTNS, die Beurteilung der Gleichgewichtskontrolle, der Dorsalflexionsfunktion, der Knieextensionsfunktion und der Kraft der unteren Extremitäten gemessen durch den Counter Movement Jump sowie einen 6-Minuten Ausdauertest und einen 10-Meter Gehgeschwindigkeitstest. Abgerundet wird das Assessment mit dem PSPS-C / PSK-K sowie dem Lebensqualitäts-Fragebogen
Resultate
Bei den Resultaten sind eindeutige Tendenzen zu sehen. Sowohl bei der Gleichgewichtskontrolle, als auch bei der Dorsalflexionsfunktion und dem 10m-Walkingtest sind signifikante Ergebnisse zur Referenzgruppe ersichtlich. Dies deutet darauf hin, dass das Assessment sehr gut geeignet ist, um Vergleiche zwischen gesunden Kindern vs. Onkologie-Kinder vs. Polyneuropathie-Kinder zu erstellen. Das Assessment ist klinisch umsetzbar und wichtige Erkenntnisse wurden gewonnen.
Schlussfolgerung
Das Assessment ist klinisch umsetzbar und gut geeignet, um Vergleiche zwischen gesunden Patienten vs. Onkologie Patienten vs. Polyneuropathie-Patienten herzustellen und die Therapie frühzeitig anpassen zu können. Mehr Patienten sind notwendig, um die Erkenntnisse zu bestätigen. In der Schweiz und Deutschland gehen diesbezüglich Zentren auf. Der Weg ist geebnet
Handgrip Strength and Two-Type Exercise: Association and Impact on Psychological Wellbeing in High-Grade Glioma Patients
No full textBackground: Regular exercise is believed to positively impact the mental well-being of cancer patients. There is a growing body of literature demonstrating a correlation between hand grip strength (HGS) and psychological well-being. Limited data exists for high-grade glioma (HGG) patients post-resection and radiochemotherapy. This randomized control study compared strength and endurance training to an active control group, assessing their influence on mental well-being. Additionally, the correlation between HGS and participant’s mental well-being was investigated.
Methods: A total of 10 participants (mean age = 56 years, 50% male) were enrolled. Following tumor resection, participants were randomized during adjuvant radiotherapy and/or chemotherapy. The three conditions were as follows: active control group (n = 3), strength training (n = 3), and endurance training (n = 4). At baseline, after three weeks and after six weeks, participants were interviewed and assessed. The evaluation included self-administered questionnaires and expert assessments to determine perceived stress, fatigue, anxiety, fatigue, insomnia and depressive symptoms. HGS was assessed with a handgrip strength test.
Results: The results of the present study need to be interpreted considering the limited number of participants. The findings suggest that during radiochemotherapy, both exercise interventions reduced stress levels, while strength training reduced depressive symptoms and anxiety as well. HGS was found to be inversely correlated with psychological wellbeing. The endurance group showed the most correlation with stress, sleep and depression.
Conclusion: During radiochemotherapy, both exercise interventions demonstra-ted stress reduction. Strength training demonstrated benefits in reducing depressive symptoms and anxiety, emphasizing its potential in holistic patient care.
The inverse correlation between HGS and psychological well-being underscores the importance of physical fitness in this context, while the distinct correlations in the endurance group emphasizes the nuanced impact of different exercise approaches on psychological well-being
Auswirkung einer einjährigen telefonbasierten Lebensstilintervention auf den HbA1c, die objektive körperliche Aktivität und die Medikation bei Personen mit Diabetes Mellitus Typ 2
No full textDiabetes Mellitus Typ 2 (DMT2) ist eine weitverbreitete chronische Stoffwechselerkrankung, die mit einem erhöhten Blutzuckerspiegel aufgrund eines Insulinmangels einhergeht. Komplikationen können durch einen gesunden Lebensstil vorgebeugt oder verzögert werden, weshalb die Beratung zu einem gesünderem Lebensstil nebst der medikamentösen Behandlung zur Diabetestherapie gehört. Da die Implementierung eines gesünderen Lebensstils herausfordernd ist, braucht es bewährte Methoden zu dessen Förderung. Die db-coach-Intervention als einjährige telefonbasierte Lebensstilberatung stellt eine Methode dar, welche im Rahmen dieser Arbeit auf Veränderung des HbA1c, körperliche Aktivität und Medikamenten-Verordnung untersucht wurde. Die Studie wurde bei deutschsprachigen Schweizer Personen in Form einer monozentrischen, pragmatischen, zwei-armig randomisiert kontrollierten Intervention durchgeführt. Alle Studienteilnehmenden führten die standardmässige Behandlung für DMT2 fort und erhielten Zugang zu einer Smartphone- und Web-basierten App. Die Interventionsgruppe (IG) erhielt zusätzlich während einem Jahr eine telefonbasierte Lebensstilberatung. Vor-, während- und nach der Intervention wurde der HbA1c, die körperliche Aktivität sowie die Medikamenten-Verordnung erhoben und anschliessend anhand linear gemischten Modellen ausgewertet. Anhand der Analysen wurde aufgezeigt, dass sich der HbA1c in beiden Gruppen gesenkt hat, sich jedoch die beiden Gruppen nicht voneinander unterschieden. Bei der körperlichen Aktivität wurde ersichtlich, dass die IG ihre körperliche Aktivität im Vergleich zur Kontrollgruppe (KG) steigern konnte, jedoch unterschieden sich die Gruppen nicht eindeutig von einander. Anhand der Analyse der Medikation konnte keine mittleren Gruppenunterschiede festgestellt werden. Insgesamt gab es keine signifikanten Effekte in Bezug auf den HbA1c, die objektive körperliche Aktivität und die Medikation. Um die gefunden Tendenzen zu bestätigen und auf die statistische Signifikanz zu überprüfen, braucht es weitere Studien
Combining an artificial metathase with a fatty acid decarboxylase in a whole cell for cycloalkene synthesis
No full textArtificial metalloenzymes (ArMs) offer powerful tools to catalyse new-to-nature reactions. Accordingly, ArMs offer great potential to complement natural enzymes in concurrent cascade reactions. For in cellulo applications, however, the abundance of thiols in the cytosol of aerobic organisms limits the use of ArMs that rely on precious-metal cofactors. To overcome this limitation, compartmentalization of ArMs either in the periplasm or on the surface of Escherichia coli has shown promise. Here we report on our efforts to combine a surface-displayed artificial metathase with UndB, an inner-membrane decarboxylase. The resulting concurrent cascade converts medium-chain dicarboxylates to cyclic alkenes. To optimize the cascade, we evolved both enzymes independently and fine-tuned their expression levels. Compared with the wild-type whole-cell enzyme cascade, the yield of the engineered strain was improved by > 75-fold for the conversion of sebacic acid to cyclohexene. Combining natural and artificial metalloenzymes thus offers a promising strategy for whole-cell biocatalysis and synthetic biology to catalyse new-to-nature concurrent cascade reactions
Structural and functional characterization of the teichoic acid flippase TacF from S. pneumoniae
No full textStreptococcus pneumoniae, a Gram-positive bacterium, stands as a significant contributor to mortality among children under 5 years worldwide. Beyond causing community-acquired pneumonia, it can induce severe and fatal infections in adults, including meningitis and septicemia. Recognizing the escalating multi-drug resistance issue, the World Health Organization (WHO) incorporated S. pneumoniae into the list of 12 priority pathogens necessitating the development of novel antibiotics in 2017.
As a Gram-positive bacterium, S. pneumoniae possesses a robust cell wall primarily composed of peptidoglycan and teichoic acids. Teichoic acids manifest as glycopolymers, classified as lipoteichoic acids (LTA) when bound to a lipidic carrier or wall teichoic acids (WTA) when covalently linked to peptidoglycan in the cell wall. In S. pneumoniae, teichoic acids comprise repeating units of 2-acetamido-4-amino-2,4,6-trideoxygalactose (AATGal), glucose (Glc), ribitol-5-phosphate (RboP), and two molecules of N-acetylglucosamine (GalNAc). Phosphorylcholine moieties, added by the LicC protein, adorn the GalNAc moieties.
Choline-binding proteins (CBP), featuring a choline-binding domain (CBD), interact with phosphorylcholine moieties in teichoic acids (TA) located either in the cell wall (WTA) or plasmatic membrane (LTA). These proteins play various roles, including immune system evasion, host cell recognition, and biofilm formation. Despite the diverse functions attributed to CBPs, the biosynthetic pathway of TA in S. pneumoniae remains incompletely understood, particularly regarding the translocation process towards the extracellular leaflet of the membrane.
TacF, a member of the prokaryotic polysaccharide transporter (PST) family within the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily of transporters, is the putative protein responsible for translocating TA. Its homology model suggests a protein folding similar to the lipid II transporter MurJ of the peptidoglycan biosynthetic pathway. However, the mechanism of lipid translocation in the MOP superfamily is poorly elucidated and there are no structures available of TA flippases for this family. In this study, we present, for the first time, the cryo-electron Microscopy (cryo-EM) structure of TacF at a resolution of 3.5Å in an inward-open conformation. Notable structural features, such as a hydrophobic groove, aromatic residues in the cavity, and ion binding sites, were identified and deemed crucial for the function of the protein.
Through a combination of functional assays in vitro, molecular dynamics (MD) simulations, and in vivo approaches, we propose the TA binding sites and the transport mechanism of TacF. A method for synthesizing and purifying NBD-labelled TA was developed for functional assays. These findings not only lay the foundation for understanding other MOP superfamily lipid transporters but also provide insights for targeted structure- and function-based drug design against S. pneumoniae
Ist der Monotheismus inkarnationsfähig? Eine religionsgeschichtliche Untersuchung zur Verhältnisbestimmung zwischen frühjüdischem Monotheismus und der frühsten Christologie im Neuen Testament
No full textGeteilte Vorstellungen : Selbstverortungen Venedigs zwischen Levante, Lagune und 'terra ferma' 1453–1600
No full textTime since liver transplant and immunosuppression withdrawal outcomes: Systematic review and individual patient data meta-analysis
No full textBackground & Aims
Successful immunosuppression withdrawal (ISW) is possible for a subfraction of liver transplant (LT) recipients but the factors that define the risk of ISW failure are largely unknown. One candidate prognostic factor for ISW success or operational tolerance (OT) is longer time between LT and ISW which we term “pre-withdrawal time”. To clarify the impact of pre-withdrawal time span on subsequent ISW success or failure, we conducted a systematic review with meta-analysis.
Methods
We systematically interrogated the literature for LT recipient ISW studies reporting pre-withdrawal time. Eligible articles from Embase, Medline, and the Cochrane Central Register of Controlled Trials were used for backward and forward citation searching. Pre-withdrawal time individual patient data (IPD) was requested from authors. Pooled mean differences and time-response curves were calculated using random-effects meta-analyses.
Results
We included 17 studies with 691 patients, 15 of which (620 patients) with IPD. Study-level risk of bias was heterogeneous. Mean pre-withdrawal time was greater by 427 days [95% confidence interval (CI) 67–788] in OT compared to non-OT patients. This increase was potentiated to 799 days (95% CI 369–1229) or 1074 days (95% CI 685–1463) when restricting analysis to adult or European study participants. In time-response meta-analysis for adult or European ISW candidates, likelihood of OT increased by 7% (95% CI 4–10%) per year after LT (GRADE low- and moderate-certainty of evidence, respectively).
Conclusions
Our data support the impact of pre-withdrawal time in ISW decision-making for adult and European LT recipients. PROSPERO REGISTRATION: CRD42021272995
Muscle Activity and Kinematics During Three Hamstring Strengthening Exercises Compared to Sprinting: A Cross-Sectional Study
No full textBackground: During sprinting, the biceps femoris long head predominantly gets injured, while hamstring strengthening exercises predominantly activate the semitendinosus more
effectively. Understanding how joint dominance influences hamstring activity may offer clarity on the appropriate exercise selection in strengthening programs.
Purpose: This study compared 3 hip-dominant hamstring exercises (the rocker, perpetuum mobile fast and slow; PMfast and PMslow) and the Nordic Hamstring exercise (NHE) on their potential to simulate sprint-like activity and kinematics.
Methods: Muscle activity of the posterior kinetic chain (mm. biceps femoris, semitendinosus, gluteus maximus and gastrocnemius medialis) was measured with surface electromyography (sEMG) during every exercise and treadmill running at 75% of the individual maximal sprint velocity in 8 male athletes (age: 24.0 years ± SD 2.9; body mass: 76.8 kg ± 7.7; height: 1.79 m ± 0.08). sEMG data was normalized to maximal sprinting. 3D-motion capture was employed to assess hip and knee angles.
Results: This study revealed higher activity of the hamstrings for the explosive exercises ranging from 63.9% [95%CI: 56.3-71.5%] (rocker) to 49.0% [95%CI: 40.4-57.6%] (PMfast) vs. 34.0% [95%CI: 29.1-38.9%] (NHE) to 32.1% [95%CI: 26.9-37.3%] (PMslow). The rocker especially showed highest hamstring and m. gluteus maximus activity. M. biceps femoris consistently showed higher activity than m. semitendinosus across all exercises in peak (mean difference: 0.16, [95%CI: 0.07-0.26]) and average (mean difference: 0.06, [95%CI: 0.01-0.11]) activity. PMfast, PMslow and NHE demonstrated lower hip flexion angle of peak hamstring activity than the rocker and high-speed running and every exercise showed lower hamstring elongation stress than during high-speed running.
Discussion: Hamstring activity is comparable to high-intensity treadmill running for NHE and PMslow, and higher for the rocker and PMfast. M. gluteus maximus activity varied, with the rocker and PMfast showing higher activity than in sprinting. All examined exercises demonstrated their
peak activity at short hamstring muscle length
Learning from the Past: The Role of Personal Experiences in Artificial Stock Markets
Full text linkRecent survey evidence suggests that investors form beliefs about future stock returns by predominantly extrapolating their own experience: They overweight returns they have personally experienced while underweighting returns from earlier years and consequently expect high (low) stock market returns when they observe bullish (bearish) markets in their lifespan. Such events are difficult to reconcile with the existing models. This paper introduces a simple agent-based model for simulating artificial stock markets in which mean-variance optimizing investors have heterogeneous beliefs about future capital gains to form their expectations. Using this framework, I successfully reproduce various stylized facts from the empirical finance literature, such as under diversification, the predictive power of the price-dividend ratio, and the autocorrelation of price changes. The experimental findings show that the most realistic market scenarios are produced when agents have a bias for recent returns. The study also established a link between under diversification of investor portfolios and personal experiences