∆9^{9}-Tetrahydrocannabinol Increases Growth Factor Release by Cultured Adipose Stem Cells and Adipose Tissue in vivo

BACKGROUND Because of its biocompatibility and its soft and dynamic nature, the grafting of adipose tissue is regarded an ideal technique for soft-tissue repair. The adipose stem cells (ASCs) contribute significantly to the regenerative potential of adipose tissue, because they can differentiate into adipocytes and release growth factors for tissue repair and neovascularization to facilitate tissue survival. The present study tested the effect of administering a chronic low dose of ∆$^{9}$-tetrahydrocannabinol (THC) on these regenerative properties, in vitro and in vivo. METHODS Human ASCs were exposed to increasing concentrations of THC. Resazurin conversion was applied to investigate the effect on metabolic activity, cell number was assessed by crystal violet staining, tri-linear differentiation was evaluated by specific colorimetric approaches, and the release of growth factors was analyzed by ELISA. Two groups of mice were treated daily either with a low dose of THC (3 mg/kg) or a vehicle solution. After 3 weeks, adipose tissue was obtained from excised fat deposits, homogenized and tested for growth factor contents. RESULTS THC decreased ASC proliferation but increased metabolic activity as well as adipogenic and chondrogenic differentiation. A low concentration of THC (1 µM) enhanced the growth factor release by ASCs. The concentration of these cytokines was also increased in adipose tissue of mice treated with THC. CONLUSION Our results indicate that chronic activation of the endocannabinoid system promoted differentiation and growth factor release of ASCs, which could be of specific value for enhancing the regenerative potential of adipose tissue

Severe alpha-1 antitrypsin deficiency is associated with a higher risk of complications after first decompensation than other aetiologies of cirrhosis

Advanced chronic liver disease; Ascites; Hepatic encephalopathyEnfermedad hepática crónica avanzada; Ascitis; Encefalopatía hepáticaMalaltia hepàtica crònica avançada; Ascites; Encefalopatia hepàticaBackground & Aims Alpha-1 antitrypsin deficiency (AATD) causes/predisposes to advanced chronic liver disease. However, the role of the SERPINA1 Pi∗ZZ genotype in patients with decompensated cirrhosis is unclear. Thus, we evaluated the impact of the Pi∗ZZ genotype on the disease course after the first hepatic decompensation event. Methods We retrospectively included 59 adults with decompensated cirrhosis and severe AATD (Pi∗ZZ) from 12 European tertiary care centres. First decompensation was considered as baseline. To compare the course of AATD to other cirrhosis aetiologies, we applied propensity score matching for Child-Turcotte-Pugh (CTP) score as well as age/sex. Patients were followed until further decompensation, liver transplantation or liver-related death. Results Most patients were male (74.6%), with a mean age of 55 years. The most common type of first decompensation was ascites (n = 40; 67.8%), followed by variceal bleeding (n = 13; 22.0%) and overt hepatic encephalopathy (n = 6; 10.2%). Median CTP and MELD (model for end-stage liver disease) scores at first decompensation were 8 and 14, respectively. Median MELD scores were 16 and 20 points at listing and liver transplantation (median time on list: 2.9 [IQR 1.1-7.2] months), respectively. Patients with other aetiologies (subdistribution hazard ratio: steatotic liver disease: 0.62, 95% CI 0.44-0.88, p = 0.007; abstinent alcohol-associated liver disease: 0.50, 95% CI 0.35-0.71, p <0.001; hepatitis C virus-associated cirrhosis: 0.56, 95% CI 0.37-0.83, p = 0.004) had a significantly lower risk of further hepatic decompensation, liver transplantation, or liver-related death, compared to those with Pi∗ZZ. Exchanging further decompensation with acute-on-chronic liver failure yielded similar results. Conclusion Our study defines the course of decompensated cirrhosis in patients with severe AATD (Pi∗ZZ), who are particularly prone to complications of cirrhosis and exhibit a more progressive disease course than those with cirrhosis of other aetiologies. Impact and implications Alpha-1 antitrypsin deficiency is an inherited disease that affects the lung and the liver. Carrying two severely dysfunctional copies of the alpha-1 antitrypsin gene may cause advanced chronic liver disease/cirrhosis. Affected individuals with a first complication of cirrhosis are more prone to developing further liver-related events (including multiorgan dysfunction) and requiring liver transplantation (which cures the inherited liver disease) compared to patients who have similarly advanced liver disease. These findings should prompt the development of disease-modifying treatments and early listing for liver transplantation.This work was supported by the DFG grants STR1095/6-1, SFB 1382 (ID 403224013), unrestricted research grants from CSL Behring (all to P.S.) and the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (PTD 1-3) (to M.F. and P.S.)

Energiepreisanstieg 2022, Trinkwasser-Temperatursenkung und Legionellose-Inzidenz – sind Zusammenhänge erkennbar?

Legionellen sind im Wasser vorkommende Umweltkeime, die sich insbesondere bei einer Wassertemperatur zwischen 25 und 45° C gut vermehren und auch technische Trinkwasserinstallationen besiedeln. Oberhalb von 55° C wird ihr Wachstum gehemmt. Im Rahmen der Energiekrise im Jahr 2022 kam es zu einem deutlichen Anstieg der Energiepreise, was auch die Erwärmung des Trinkwassers verteuerte. Im Projekt TESLI (Temperatursenkung und Legionellose-Inzidenz) wurde untersucht, ob es im Jahr 2022 zu Veränderungen der Trinkwassertemperatur kam und ob in dem Zusammenhang ein Inzidenzanstieg bei Fällen von Legionärskrankheit zu beobachten war. Dargestellt wird, wie sich die mittleren Trinkwassertemperaturen im zeitlichen Verlauf verhielten und wie hoch der Anteil der Haushalte mit heruntergestellter Temperatur war. Diese Daten wurden auf Bundeslandebene mit der Inzidenz von Legionärskrankheitsfällen korreliert

Recast Drinking Water Directive - State of play: Guidance note for the analysis of microbiological parameters

The quality of drinking water in the European Union is ensured by measuring parameters established in the recast of the Drinking Water Directive (DWD) 2020/2184. Respect to the former Directive, microbiological parameters have been extended to additionally cover somatic coliphages as an indicator of removal efficiency following water treatment and Legionella as a parameter for the risk assessment in buildings. Implementation of these parameters and their transposition is of utmost importance for the Member States to ensure an adequate level of protection for human health. However, existing standardised methods used to measure the new microbiological parameters present technical drawbacks. Alternative methods may provide a solution to overcome the technical limitations of standardised methods and to significantly reduce time to results allowing an early action in case of detected contamination. According to DWD 2020/2184, such methods can be implemented for analysing somatic coliphages and Legionella if their reliability is at least equal to that of the standard method. The Guidance Note presents an overview of current and novel methods for testing the new microbiological parameters and provides recommendation on harmonising the choice of alternative methods at EU level.JRC.D.2 - Water and Marine Resource

Einfluss der häuslichen Trinkwasser-Installation auf das Risiko, an Legionärskrankheit zu erkranken

Der Grad der Trinkwasserkontamination mit Legionellen ist ein guter Indikator für den technischen Zustand einer Trinkwasser-Installation. Allerdings ist unklar, ob er auch eine prädiktive Bedeutung für das Auftreten von Legionärskrankheit hat. Aus den Ergebnissen der Berliner LeTriWa-Studie ließ sich ableiten, dass bei dem größten Teil der Fälle von ambulant erworbener Legionärskrankheit häusliches Trinkwasser eine vermutliche oder wahrscheinliche Rolle spielt. Es wird nun untersucht, inwiefern Patientinnen und Patienten mit ambulant erworbener Legionärskrankheit von einer Trinkwasser-Installation versorgt werden, die nach Trinkwasserverordnung untersuchungspflichtig ist, bzw. ob ihrer Erkrankung eine erhöhte Legionellenkonzen¬tration im Trinkwasser vorausging.Peer Reviewe

Building generic anatomical models using virtual model cutting and iterative registration

Article deposited according to publisher policy posted on SHERPA/RoMEO, 30/07/2010.YesFunding provided by the Open Access Authors Fund

Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype)

BACKGROUND & AIMS Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients

Wahrscheinlicher Fall einer Reinfektion durch Legionella pneumophila

In Deutschland wird die Legionärskrankheit in der Regel durch die Spezies Legionella (L.) pneumophila verursacht. Von rezidivierenden Fällen der Legionärskrankheit wird selten berichtet, sie sind entweder auf eine zweite Infektion (Reinfektion) oder auf einen Rückfall (Wiederaufflammen; engl. relapse) einer zwischenzeitlich ruhenden/gebesserten, aber nicht völlig ausgeheilten Erkrankung zurückzuführen. Wir berichten über einen Fall einer rezidivierenden Legionärskrankheit bei einer 86-jährigen Patientin mit einer Erkrankung durch L. pneumophila Serogruppe 1, monoklonaler Antikörpersubtyp Knoxville, Sequenztyp unbekannt. Zwischen den beiden, mehrere Monate auseinander liegenden, Krankheitsepisoden hatte sich die Patientin vollständig erholt. Im Trinkwasser der Wohnung der Patientin konnten wir L. pneumophila Serogruppe 1, monoklonaler Antikörpersubtyp Knoxville, Sequenztyp 182, nachweisen. Nach der ersten Krankheitsepisode wurde die Exposition gegenüber kontaminiertem Trinkwasser durch Einsatz von Wasserfiltern unterbrochen. Die Filter wurden später wegen des geringen Wasserdrucks entfernt, nur wenige Wochen später trat die zweite Krankheitsepisode auf. Es ist unklar, ob eine immunologische Veranlagung zu diesem Fall einer wahrscheinlichen Reinfektion der Legionärskrankheit beigetragen hat. Klinische, mikrobiologische und epidemiologische Informationen lassen darauf schließen, dass es sich bei der zweiten Episode um eine erneute Infektion handelte. Im Falle einer rezidivierenden Legionärskrankheit ist eine möglichst vollständige Sammlung von Patienten- und Wasserproben erforderlich, um zu entscheiden, ob es sich um einen Rückfall oder eine Reinfektion handelt, um die Infektionsquelle zu identifizieren und weitere Hinweise für die Rolle einer immunologischen Prädisposition zu erhalten