A double-blind, randomized, sham-controlled study of Targeted Lung Denervation in patients with moderate to severe COPD

Background: Targeted Lung Denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung. Aim: Evaluate safety and efficacy of TLD + tiotropium compared to sham bronchoscopy + tiotropium at 6 months. Methods: TLD was performed in stable COPD patients (FEV1/FVC<0.7, FEV1 30-60% predicted, CAT≥10 or mMRC≥2) in a double-blind, 1:1 randomized, sham-controlled, multicenter (n=15) study (NCT02058459) using a novel lung denervation system (Nuvaira, Inc., USA). Primary endpoint was % of patients with respiratory adverse events (respiratory failure; pneumonia; COPD exacerbation; influenza; respiratory infection; worsening bronchitis; worsening dyspnea; tachypnea; wheezing; or airway defects requiring therapeutic intervention) between 3 and 6 months. Secondary endpoints included SGRQ, TDI, EQ-5D, spirometry, and plethysmography. Results: 82 patients (FEV1 41.6±7.4 %pred., 50.0% male, age 63.7±6.8 yrs) were randomized with 81 patients completing 6-month follow-up. There were no deaths or treatment related AEs requiring therapeutic interventions. The primary endpoint was met with pre-defined respiratory AEs in 71% of sham and 32% of treatment patients between 3 and 6 months (p=0.0008). Change at 6 months compared to baseline in sham vs treatment arms: SGRQ -3.8±13.8 vs -8.3 ± 12.6, TDI -1.5±3.7 vs +0.25±3.2, EQ-5D VAS 3.1±21.5 vs 9.1±22.5, FEV1 86±180 vs 127±201 ml, FVC 147±361 vs 240±390 ml, RV -93±926 vs -322±760 ml. Conclusion: TLD + tiotropium demonstrated a significant reduction in respiratory adverse events and trends toward improved quality of life, dyspnea, and pulmonary function testing when compared to sham + tiotropium

Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism

International audienceOutside In Acquisition and analysis of large data sets promises to move us toward a greater understanding of the mechanisms by which biological systems are dynamically regulated to respond to external cues. Now, two papers explore the responses of a bacterium to changing nutritional conditions (see the Perspective by Chalancon et al. ). Nicolas et al. (p. 1103 ) measured transcriptional regulation for more than 100 different conditions. Greater amounts of antisense RNA were generated than expected and appeared to be produced by alternative RNA polymerase targeting subunits called sigma factors. One transition, from malate to glucose as the primary nutrient, was studied in more detail by Buescher et al. (p. 1099 ) who monitored RNA abundance, promoter activity in live cells, protein abundance, and absolute concentrations of intracellular and extracellular metabolites. In this case, the bacteria responded rapidly and largely without transcriptional changes to life on malate, but only slowly adapted to use glucose, a shift that required changes in nearly half the transcription network. These data offer an initial understanding of why certain regulatory strategies may be favored during evolution of dynamic control systems

Effect of Neurexan on the pattern of EEG frequencies in rats

<p>Abstract</p> <p>Background</p> <p>Various medications of natural origin have effectively treated stress-related disorders, such as sleep disturbances and agitated conditions. The efficacy of Neurexan, a multicomponent, low-dose medication, has been demonstrated in observational studies, but its exact mechanism of action has not been determined.</p> <p>Methods</p> <p>To characterize the effects of Neurexan on the central nervous system, we analyzed the spectral frequencies of field potentials in four rat brain areas after a single oral administration of Neurexan. Different doses of Neurexan were tested within a crossover design, and effects were compared with vehicle control.</p> <p>Results</p> <p>Significant effects were observed with 0.5 tablets of Neurexan, predominantly on δ- and θ-waves in the frontal cortex and reticular formation (<it>P</it> < 0.01). In the reticular formation, significant changes of δ- and θ-waves occurred as early as during the first hour after administration. The time course revealed a significant and longer-lasting increase of δ- and θ-waves in the frontal cortex and reticular formation, whereas other spectral frequencies were only transiently affected in the frontal cortex, reticular formation, and striatum.</p> <p>Conclusion</p> <p>In conclusion, this study demonstrated that the low-dose medication Neurexan influences central nervous system activity in rats. The resulting electroencephalographic profile of Neurexan shows several similarities with those of other calming agents, such as Valeriana and Passiflora, suggesting a potential benefit of Neurexan for patients with stress-related disorders. Moreover, this report demonstrates that electroencephalographic signatures are also valid biomarkers for the assessment of low-dose medications, such as Neurexan.</p

Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.publishedVersionPeer reviewe

LifeTime and improving European healthcare through cell-based interceptive medicine

AUTEURS : LifeTime Community Working GroupsInternational audienceHere we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade