94 research outputs found

    Identifying Responders and Exploring Mechanisms of Action of the Endobronchial Coil Treatment for Emphysema

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    Background: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. Objectives: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. Methods: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. Results: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV1] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV1, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. Conclusions: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes

    Population-wide cerebellar growth models of children and adolescents

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    In the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using a total of 7240 neuroimaging scans from 4862 individuals, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence (age range: 6–17 years), an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.</p

    A Plasmodium-Encoded Cytokine Suppresses T-Cell Immunity During Malaria

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    The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs

    An integrated modelling approach to derive the grey water footprint of veterinary antibiotics

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    Water pollution by veterinary antibiotics (VAs) resulting from livestock production is associated with severe environmental and human health risks. While upward trends in global animal product consumption signal that these risks might exacerbate toward the future, VA related water pollution is currently insufficiently understood. To increase this understanding, the present research assesses processes influencing VA pollution from VA administration to their discharge into freshwater bodies, using an integrated modelling approach (IMA). For the VAs amoxicillin, doxycycline, oxytetracycline, sulfamethazine, and tetracycline we estimate loads administered to livestock, excretion, degradation during manure storage, fate in soil and transport to surface water. Fate and transport are modelled using the VA transport model (VANTOM), which is fed with estimates from the Pan-European Soil Erosion Risk Assessment (PESERA). The grey water footprint (GWF) is used to indicate the severity of water pollution in volumetric terms by combining VA loads and predicted no effect concentrations. We apply our approach to the German-Dutch Vecht river catchment, which is characterized by high livestock densities. Results show a VA mass load decrease larger than 99% for all substances under investigation, from their administration to surface water emission. Due to metabolization in the body, degradation during manure storage and degradation in soil, VA loads are reduced by 45%, 80% and 90% on average, respectively. While amoxicillin and sulfamethazine dissipate quickly after field application, significant fractions of doxycycline, oxytetracycline and tetracycline accumulate in the soil. The overall Vecht catchment's GWF is estimated at 250,000 m3 yr−1, resulting from doxycycline (81% and 19% contribution from the German and Dutch catchment part respectively). Uncertainty ranges of several orders of magnitude, as well as several remaining limitations to the presented IMA, underscore the importance to further develop and refine the approach
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