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Characterization of rostral brainstem nuclei controlling locomotion directionality
No full textRecent studies have uncovered specific functions for brainstem nuclei based on mouse genetics and viral tracing technologies. In this thesis, we characterize pre-motor nuclei of the rostral brainstem and interogate their role in specific full body locomotor functions
Improving coverage of antenatal iron and folic acid supplementation and malaria prophylaxis through targeted information and home deliveries in Côte d'Ivoire: a cluster randomised controlled trial
Get PDFINTRODUCTION: Coverage of antenatal iron and folic acid (IFA) supplementation and malaria chemoprophylaxis remains low in many low-income and middle-income settings. We assessed the effectiveness of personal information (INFO) sessions and personal information session plus home deliveries (INFO+DELIV) to increase coverage of IFA supplementation and intermittent preventive treatment in pregnancy (IPTp), and their effectiveness on postpartum anaemia and malaria infection. METHODS: We included 118 clusters randomised to a control (39), INFO (39) and INFO+DELIV (40) arm, in a trial conducted between 2020 and 2021 with pregnant women (age >/=15 years) in their first or second trimester of pregnancy in Taabo, Cote d'Ivoire. We used generalised linear regression models to assess intervention impact in postpartum anaemia and malaria parasitaemia, and displayed resulting estimates as prevalence ratios. RESULTS: Overall, 767 pregnant women were enrolled and 716 (93.3%) were followed up after delivery. Neither intervention had an impact on postpartum anaemia, with estimated adjusted prevalence ratios (aPRs) of 0.97 (95% CI 0.79 to 1.19, p=0.770) for INFO and 0.87 (95% CI 0.70 to 1.09, p=0.235) for INFO+DELIV. While INFO had no effect on malaria parasitaemia (aPR=0.95, 95% CI 0.39 to 2.31, p=0.915), INFO+DELIV reduced malaria parasitaemia by 83% (aPR=0.17, 95% CI 0.04 to 0.75, p=0.019). No improvements in antenatal care (ANC) coverage (aPR=1.05, 95% CI 0.81 to 1.36, p=0.692), IFA (aPR=2.00, 95% CI 0.89 to 4.46, p=0.093) and IPTp (aPR=1.03, 95% CI 0.87 to 1.21, p=0.728) compliance were found for INFO. INFO+DELIV increased ANC attendance (aPR=1.35, 95% CI 1.02 to 1.78, p=0.037) and compliance with IPTp (aPR=1.60, 95% CI 1.41 to 1.80, p<0.001) and IFA recommendations (aPR=7.06, 95% CI 3.68 to 13.51, p<0.001). CONCLUSIONS: INFO+DELIV can substantially increase compliance with IFA supplementation and improve malaria prevention. However, the increases in IFA supplementation are likely insufficient to address the prevalence of often severe anaemia in this population. TRIAL REGISTRATION NUMBER: NCT04250428
Effect of residential relocation on environmental exposures in European cohorts: an exposome-wide approach
Get PDFResidential relocation is increasingly used as a natural experiment in epidemiological studies to assess the health impact of changes in environmental exposures. Since the likelihood of relocation can be influenced by individual characteristics that also influence health, studies may be biased if the predictors of relocation are not appropriately accounted for. Using data from Swedish and Dutch adults (SDPP, AMIGO), and birth cohorts (BAMSE, PIAMA), we investigated factors associated with relocation and changes in multiple environmental exposures across life stages. We used logistic regression to identify baseline predictors of moving, including sociodemographic and household characteristics, health behaviors and health. We identified exposure clusters reflecting three domains of the urban exposome (air pollution, grey surface, and socioeconomic deprivation) and conducted multinomial logistic regression to identify predictors of exposome trajectories among movers. On average, 7% of the participants relocated each year. Before relocating, movers were consistently exposed to higher levels of air pollution than non-movers. Predictors of moving differed between the adult and birth cohorts, highlighting the importance of life stages. In the adult cohorts, moving was associated with younger age, smoking, and lower education and was independent of cardio-respiratory health indicators (hypertension, BMI, asthma, COPD). Contrary to adult cohorts, higher parental education and household socioeconomic position were associated with a higher probability of relocation in birth cohorts, alongside being the first child and living in a multi-unit dwelling. Among movers in all cohorts, those with a higher socioeconomic position at baseline were more likely to move towards healthier levels of the urban exposome. We provide new insights into predictors of relocation and subsequent changes in multiple aspects of the urban exposome in four cohorts covering different life stages in Sweden and the Netherlands. These results inform strategies to limit bias due to residential self-selection in epidemiological studies using relocation as a natural experiment
Defining risk-based monitoring frequencies to verify the performance of water treatment barriers
No full textPreventing failures of water treatment barriers can play an important role in meeting the increasing demand for microbiologically safe water. The development and integration of failure prevention strategies into quantitative microbial risk assessment (QMRA) offer opportunities to support the design and operation of treatment trains. This study presents existing failure models and extends them to guide the development of risk-based operational monitoring strategies. For barriers with rapid performance loss, results show that a failure of 15 s should be reliably detected to verify a log reduction value (LRV) of 6.0; thus, detecting and remediating these failures may be beyond current technology. For chemical disinfection with a residual, failure durations in order of minutes should be reliably detected to verify a LRV of 6.0. Short-term failures are buffered because the disinfectant residual concentration sustains a partial reduction performance. Therefore, increasing the contact time and hydraulic mixing reduces the impact of failures. These findings demonstrate the importance of defining precise frequencies to monitor barrier performances during operation. Overall, this study highlights the utility of process-specific models for developing failure prevention strategies for water safety management
Anti-UV the Hippo Way
Get PDFThe hippopotamus secretes a liquid from its skin that may act both as a sunscreen and an antibioti
Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo
Get PDFAdipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand
Information-to-work conversion in single-molecule experiments: From discrete to continuous feedback
Get PDFWe theoretically investigate the extractable work in single molecule unfolding-folding experiments with applied feedback. Using a simple two-state model, we obtain a description of the full work distribution from discrete to continuous feedback. The effect of the feedback is captured by a detailed fluctuation theorem, accounting for the information aquired. We find analytical expressions for the average work extraction as well as an experimentally measurable bound thereof, which becomes tight in the continuous feedback limit. We further determine the parameters for maximal power or rate of work extraction. Although our two-state model only depends on a single effective transition rate, we find qualitative agreement with Monte Carlo simulations of DNA hairpin unfolding-folding dynamics
Manganese Transfer Hydrogenases Based on the Biotin-Streptavidin Technology
Get PDFArtificial (transfer) hydrogenases have been developed for organic synthesis, but they rely on precious metals. Native hydrogenases use Earth-abundant metals, but these cannot be applied for organic synthesis due, in part, to their substrate specificity. Herein, we report the design and development of manganese transfer hydrogenases based on the biotin-streptavidin technology. By incorporating bio-mimetic Mn(I) complexes into the binding cavity of streptavidin, and through chemo-genetic optimization, we have obtained artificial enzymes that hydrogenate ketones with nearly quantitative yield and up to 98% enantiomeric excess (ee). These enzymes exhibit broad substrate scope and high functional-group tolerance. According to QM/MM calculations and X-ray crystallography, the S112Y mutation, combined with the appropriate chemical structure of the Mn cofactor plays a critical role in the reactivity and enantioselectivity of the artificial metalloenzyme (ArMs). Our work highlights the potential of ArMs incorporating base-meal cofactors for enantioselective organic synthesis
Assoziation des kardiovaskulären Risikoprofils mit der mikro- und makrovaskulären Endothelfunktion bei Jugendlichen
No full textHintergrund:
Herz-Kreislauf-Erkrankungen sind weltweit die häufigste Todesursache. Die Messung der Endothelfunktion eignet sich als idealer Biomarker für die frühzeitige Erkennung eines erhöhten Erkrankungsrisikos und wird bereits bei Erwachsenen in der medizinischen Praxis zur kardiovaskulären (KV) Risikostratifizierung angewendet. Das Ziel dieser Masterarbeit bestand darin, die Zusammenhänge zwischen KV Risikofaktoren und Gefässmarkern der Mikro- und Makrozirkulation bei Jugendlichen zu analysieren, um die funktionellen Gefässmarker in dieser Altersgruppe potenziell einsetzen zu können.
Methoden:
Im Rahmen der 8-Jahres-Follow-Up Studie wurden Jugendliche aus dem Kanton Basel-Stadt rekrutiert. Die Studie absolvierte bei den Jugendlichen Messungen der KV Risikofaktoren und Gefässfunktionen. Neben anthropometrischen Daten, dem Blutdruck und der kardiorespiratorischen Fitness (Shuttle Run) wurde die Dilatationsfähigkeit der grossen und kleinen retinalen Gefässe mittels flussinduzierter Dilatation (FMD) und Flickerlicht induzierter Dilatation (FID) gemessen.
Resultate:
Schlussendlich konnten die Daten von 52 Jugendliche (Durchschnittsalter 15.24±0.35, 27 weiblich, 25 männlich) ausgewertet werden. Es wurde eine signifikante inverse Assoziation zwischen der FMD und der kardiorespiratorischen Fitness festgestellt (p=0.03, 95% KI: -0.10 bis -0.01). Darüber hinaus zeigten sich keine weiteren signifikanten Assoziationen. Auch zwischen den KV Risikofaktoren und der DVA konnten keine signifikanten Tendenzen gezeigt werden. Jedoch stimmten einige Tendenzen mit den Ergebnissen mit denen der Hypothesen überein, nämlich dass ein höherer Risikofaktor zu einer schlechteren Endothelfunktion führt.
Schlussfolgerungen:
Obwohl die Resultate richtige Tendenzen für den Nutzen der Messung der Endothelfunktion bei Jugendlichen aufzeigen, braucht es weiterführende Studien mit grösseren Kohorten, um signifikante Assoziationen zwischen KV Risikofaktoren und der Endothelfunktion bei Jugendlichen zu stratifizieren und somit den Vorteil der funktionellen Gefässmarkern aufzuzeigen. Ausserdem sind longitudinale Studien in diesem Bereich notwendig, damit die langfristigen prädiktiven Werte der funktionellen Gefässanalysen vom Kindes- bis hin zum Erwachsenenalter nachgewiesen werden können
Zusammenhang zwischen Muskelk raft und kardiorespiratorischer Leistungsfähigkeit bei Erwachsenen mit stabiler Herzinsuffizienz mit erhaltener Ejektionsfraktion
No full textHintergrund
Es besteht ein grosses ungedecktes Bedürfnis, eine effektive Therapie zur gezielten Behandlung von Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF) bereitzustellen. Bewegungstraining scheint die körperliche Leistungsfähigkeit und die kardiovaskuläre Funktion bei HFpEF zu verbessern. Es soll untersucht werden, inwiefern das Krafttraining in der Bewegungstherapie sinnvoll ist.
Methoden
Insgesamt 40 Proband*innen absolvierten eine zwölfwöchige Ausdauertrainingsintervention. In den ersten acht Wochen wurde zusätzlich ein Krafttraining durchgeführt. Vor und nach der Trainingsintervention wurde die VO2peak gemessen sowie die Muskelkraftwerte anhand des Counter-Movement-Jumps (relative Kraft [W/kg] und relative Leistung [N/kg]) und des Mid-Thigh-Pull (relatives Gewicht pro Kilogramm Körpergewicht [kg/kgKG]) erhoben. Die Zusammenhänge zwischen Muskelkraft und kardiorespiratorischer Leistungsfähigkeit wurden untersucht.
Ergebnisse
Es wurden vor und nach der Intervention keine signifikanten Unterschiede in der relativen Leistung (p = 0.530) und relativen Kraft (p = 0.533) festgestellt, aber eine signifikante Verbesserung um 0.2 kg/kgKG des relativen Gewichts (p = 0.001). Es gab kein signifikanter linearer Zusammenhang zwischen der relativen Leistung (p = 0.127), der relativen Kraft (p = 0.285) und des relativen Gewichts (p = 0.411) bezüglich der VO2peak. Es wurde eine signifikante positive Korrelation zwischen der Veränderung der relativen Kraft (p = 0.031) und der Veränderung der VO2peak gefunden.
Schlussfolgerung
HFpEF-Patient*innen reagieren unterschiedlich auf Ausdauer- und Krafttraining. Verbesserungen in der Muskelkraft führten nicht notwendigerweise zur verbesserten VO2peak. Dennoch gibt es vielversprechende Trends. Weitere Untersuchungen sind erforderlich, um den Nutzen von Krafttraining in Kombination mit Ausdauertraining für HFpEF-Patienten zu bestätigen