Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury

Înjured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial

BACKGROUND The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months

TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time

Intestinal IL-1β Plays a Role in Protecting against SARS-CoV-2 Infection

The intestine is constantly balancing the maintenance of a homeostatic microbiome and the protection of the host against pathogens such as viruses. Many cytokines mediate protective inflammatory responses in the intestine, among them IL-1β. IL-1β is a proinflammatory cytokine typically activated upon specific danger signals sensed by the inflammasome. SARS-CoV-2 is capable of infecting multiple organs, including the intestinal tract. Severe cases of COVID-19 were shown to be associated with a dysregulated immune response, and blocking of proinflammatory pathways was demonstrated to improve patient survival. Indeed, anakinra, an Ab against the receptor of IL-1β, has recently been approved to treat patients with severe COVID-19. However, the role of IL-1β during intestinal SARS-CoV-2 infection has not yet been investigated. Here, we analyzed postmortem intestinal and blood samples from patients who died of COVID-19. We demonstrated that high levels of intestinal IL-1β were associated with longer survival time and lower intestinal SARS-CoV-2 RNA loads. Concurrently, type I IFN expression positively correlated with IL-1β levels in the intestine. Using human intestinal organoids, we showed that autocrine IL-1β sustains RNA expression of IFN type I by the intestinal epithelial layer. These results outline a previously unrecognized key role of intestinal IL-1β during SARS-CoV-2 infection

Long-term aerosol and cloud database from correlative EARLINET-CALIPSO observations

The European Aerosol Research Lidar Network, EARLINET, performs correlative observations during CALIPSO overpasses based on a sophisticated measurement strategy since June 2006. Within a dedicated activity supported by the European Space Agency (ESA), sixteen EARLINET stations contributed about 1500 measurements during an intensive observational period from May 2008 to October 2009. From these measurements, we establish a long-term aerosol and cloud database of correlative EARLINET-CALIPSO observations. This database shall provide a basis for homogenizing long-term space-borne observations conducted with different lidar instruments operating at different wavelengths on various platforms over the next decade(s). The database is also used to study the quality and representativeness of satellite lidar cross sections along an orbit against long-term lidar network observations on a continental scale.Postprint (published version

Aerosol distribution above Munich using remote sensing techniques

Aerosols are an important part of our atmosphere. As they are very inhomogenously distributed both in time and space the estimation of their influence on the climate is very complex. So it is important to improve the knowledge about the aerosol distribution. In this study the distribution of aerosols above the region around Munich, Germany in the time period 2007 to 2010 is studied with measurements from remote sensing instruments. Thereby the main focus is set on the lidar data from the ground based lidar system MULIS of the Meteorological Institute Munich and the space lidar CALIOP onboard the satellite CALIPSO which both deliver aerosol information height resolved. As an addition and for a better comparison with previous studies, aerosol information from the AERONET Sunphotometer in Munich and the satellite spectroradiometer MODIS are used. With help of these four datasets several aerosol parameters could be studied: on average the aerosol optical depth (AOD) above the Munich region is at 1064 nm about 0.05 to 0.06, at 532 nm about 0.12 to 0.17, and at 355 nm about 0.22 to 0.28. The height of the boundary layer top decreases from 1.68 km in spring to 0.73 km in winter, while the thickness of the elevated layers is more stable (spring: 1.43 km, winter: 1.02 km). The occurrence of ELs is highest in spring (in 75 % of all measurements), and lowest in winter (36 %). Measurements of the particle linear depolarization ratio and the Ångström exponent show that the aerosols in elevated layers clearly differ from the aerosols in the PBL. Especially in spring the average EL depolarization is large (25 %) indicating transportation of strongly depolarizing aerosols like Saharan dust in the free troposphere. The dominant aerosol type in the Munich region is smoke (also called biomass burning), polluted continental can occur in high concentrations especially during summer time. Dust occurs only in rare occasions, mainly mixed with other aerosol types (polluted dust). One important finding from the comparison of the four datasets is that CALIPSO strongly underestimates the AOD. To study the significances of different causes for this, the CALIPSO extinction coefficient profiles are compared with coincidentally performed measurements of MULIS. The underestimation of the AOD above Munich by CALIPSO is mainly found to be due to the failure of the layer detection: its effect on the AOD underestimation is about 36 %. Also the wrong assumption of the lidar ratio contributes to the underestimation, though on a smaller account of about 5 %. The influence of clouds in the surroundings on the AOD is not quantifiable, but the analysis shows that clouds lead to an overestimation of the AOD. To compensate these reasons and to get detailed profiles from CALIPSO, it could be shown that -for case studies- it is very efficient to calculate the extinction coefficients from CALIPSO raw data (L1B) manually

The May/June 2008 Saharan dust event over Munich: Intensive aerosol parameters from lidar measurements

At the end of May 2008 one of the strongest Saharan dust outbreaks ever reached Central Europe. This event gave us the opportunity to extend our series of studies on Saharan dust characterization, which includes measurements near the source (SAMUMâÂÂ1, Morocco) and in the regime of mid range transport (SAMUMâÂÂ2, Cape Verde). The optical properties of the aerosol particles as a function of time and height are derived from data of the two Raman depolarizationâÂÂlidar systems MULIS and POLIS at Munich and Maisach (Germany), respectively. Measurements include the extensive properties of the particles, backscatter coefficient bp and extinction coefficient ap, and the intensive particle properties, linear depolarization ratio dp and lidar ratio Sp. All quantities are derived at two wavelengths, l = 355 nm and l = 532 nm. The focus of the study is on the intensive properties, for which we found on average dp = 0.30 at 355 nm and dp = 0.34 at 532 nm. The systematic errors were typically larger than the dpâÂÂdifference at the two wavelengths. With respect to the lidar ratio, we found Sp = 59 sr for both wavelengths, with an uncertainty range between ñ4 sr and ñ10 sr. These values are quite similar to the results from the SAMUM campaigns. Thus, our results suggest that the intensive optical properties of Saharan dust do not change significantly if the transport time is less than one week. However, more case studies in the farâÂÂrange regime are required to scrutinize this statement. To further refine conclusions with respect to the wavelength dependence of dp a further reduction of the errors is desired

Dual-wavelength linear depolarization ratio of volcanic aerosols: Lidar measurements of the Eyjafjallajökull plume over Maisach, Germany

The ash plume of the Eyjafjallajökull eruption in April 2010 offered an exceptional opportunity to assess the potential of advanced lidar systems to characterize the volcanic aerosols. Consequently, the plume was continuously observed in the framework of EARLINET. In this paper we focus on the EARLINETRaman- depolarization-lidar measurements at Maisach near Munich, Germany. From these data sets the lidar ratio Sp and the particle linear depolarization ratio dp at two wavelengths (355 nm and 532 nm) were retrieved. These quantities can be used to characterize volcanic aerosols and to establish criteria for the discrimination from other aerosol types. In the pure volcanic ash plume, observed until noon of 17 April, wavelength independent values of dp as high as 0.35 < dp < 0.38, indicating non-spherical particles, were found, and lidar ratios of 50 < Sp < 60 sr at 355 nm and 45 < Sp < 55 sr at 532 nm. Later, volcanic aerosols were mixed into the boundary layer. This mixture showed in general lower values of dp as expected from the contribution of boundary layer aerosols. Especially noteworthy is the increase of dp with wavelength, when volcanic ash was mixed with small spherical particles