Wirkung der seriellen Ganzkörperkältetherapie auf die funktionelle und funktionale Gesundheit, pro- und antiinflammatorische Zytokine und Aktivitätsparameter bei Patienten mit Rheumatoider Arthritis

In den letzten Jahren durchgeführte kleinere Studien deuten darauf hin, dass die sGKKT in einer Kryosauna bei RA-Patienten Schmerzen lindern, Entzündungswerte senken und die funktionale Gesundheit verbessern kann. Ziel der vorliegenden Studie war daher, zu untersuchen, ob sich diese Effekte, sowohl kurz- als auch mittelfristig, auch in einem größeren Kollektiv nachweisen lassen. In dieser Studie wurde eine mit Flüssigstickstoff betriebene Kryosauna (Cryomed s.r.o., Slowakei) für die sGKKT eingesetzt. Von 56 RA-Patienten, die stationär eine multimodale rheumatologische Komplextherapie (MRKT) erhielten, wurden 31 nach Randomisierung zusätzlich mit sGKKT (Interventionsgruppe - IG, 6 Behandlungen in 14 Tagen) behandelt. Vor der sGKKT (V0, baseline), nach Abschluss der sGKKT (V1) und nach 3 Monaten (V2) wurden verschiedene Aktivitäts- und Funktionsparameter (HAQ, FFbH, DAS28), Schmerzen (durch VAS und NSAID-/Analgetikaverbrauch) sowie pro- (TNF-alpha, IL-6) und antiinflammatorische Zytokine (IL-10) erfasst. Zusätzlich wurden alle Probanden der IG zum Zeitpunkt V2 zu Patientenzufriedenheit, Wirksamkeit, Wichtigkeit und subjektiver Wirkdauer befragt. In der IG kam es zu einer signifikanten Senkung von Schmerzen (VAS; p < 0,001 bzw. p < 0,003) und Krankheitsaktivität (DAS28; p < 0,001 bzw. p < 0,004) sowie signifikant gesteigerten Funktionskapazität (FFbH; p < 0,003 bzw. p < 0,046) zu den Zeitpunkten V1 und V2. Auch für TNF-alpha konnte eine signifikante Senkung zum Zeitpunkt V1 und V2 gezeigt werden (jeweils p < 0,001). IL-6 verhält sich im Beobachtungszeitraum stabil, bei IL-10 kommt es zu einer signifikanten Abnahme des Spiegels in der IG zum Zeitpunkt V2 (p < 0,036). Die Patientenselbstständigkeit (HAQ) verbesserte sich signifikant in der IG zum Zeitpunkt V2 (p < 0,001), mit signifikanten Unterschieden des HAQ-Wertes zwischen Kontrollgruppe und IG zu den Zeitpunkten V1 und V2 (p < 0,009 bzw. p < 0,017). Die sGKKT wurde in der IG als mindestens „wirksam“ und „wichtig“ bewertet, was auf hohe Akzeptanz hinweist. Passend hierzu ist eine in der IG häufiger beobachtete Reduktion von NSAID/Analgetika bis zum Zeitpunkt V2. Ein Viertel der Patienten der IG beschrieb eine subjektiv erlebte Wirkdauer von 3 Monaten. Zusammenfassend lässt sich feststellen, dass die sGKKT im Rahmen einer MRKT zu mehreren, positiven Effekten wie der Reduktion von Schmerz und Krankheitsaktivität bei RA-Patienten führt, antiinflammatorische Veränderungen auf Zytokinebene induziert und somit eine sinnvolle Ergänzung einer MRKT darstellt, um die erzielten positiven Effekte auch mittelfristig zu erhalten.Past smaller studies indicate that serial whole body cryotherapy (sWBC) in a cryosauna alleviates pain, decreases inflammatory activity and increases functional health in RA patients. Therefore, the objective of this study was to assess the short- and intermediate-term effects of sWBC in a larger patient population. In this study, a liquid nitrogen cryosauna (Cryomed s.r.o., Slovakia) was used for sWBC. After randomization, 31 out of 56 patients with RA that were treated with an in-hospital multimodal rheumatologic complex therapy (MRCT) additionally received sWBC therapy (Intervention group – IG, 6 applications in 14 days). Several parameters of disease activity and functionality (HAQ, FFbH, DAS28), pain (via VAS and consumption of NSAIDs/analgesics), and pro- (TNF-alpha, IL-6) and anti-inflammatory cytokines (IL-10) have been assessed at the following timepoints: Before sWBC (V0), after sWBC completion (V1) and after 3 months (V2). Patient-reported outcomes on treatment satisfaction, efficacy and importance of sWBC treatment, and on duration of effect were recorded after sWBC completion and after 3 months. A significant decrease in pain (VAS; p < 0.001, p < 0.003), disease activity (DAS28, p < 0.001, p < 0.004) and a significant increase in functionality (FFbH; p < 0.003, p < 0.046) were registered in the IG at timepoints V1 and V2. Additionally, a significant decrease of TNF-alpha was shown at timepoints V1 and V2 (p < 0.001 each). IL-6 levels remained stable during the study, for IL-10 a significant decrease has been noted at timepoint V2 in the IG (p < 0,036). Patient autonomy (HAQ) significantly improved in the IG at timepoint V2 (p <0.001), with significant difference of HAQ scores between control group and IG at both timepoints V1 and V2 (p < 0.009, p < 0.017). Furthermore, sWBC has been rated as not less than “efficacious” and “important” by IG subjects in this study, suggesting a high acceptance of this treatment. This result matches a more frequent reduction of analgesics in the IG up until timepoint V2. Approximately 25% of the IG subjects described an effect duration of three months after sWBC completion. In conclusion, sWBC as part of MRCT leads to a number of beneficial effects such as reduction of pain and disease activity in RA patients and therefore constitutes a useful supplement of MRCT to preserve its positive therapeutic effects in the medium term

Statements

Jutta Brückner  Nico HofmannHerbert AchternbuschChristian Wagne

Historical Spruce Abundance in Central Europe: A Combined Dendrochronological and Palynological Approach

Spruce is the most cultivated tree species in modern forestry in Central Europe, since it has the ability to grow on many soil types with profitable biomass accumulation. However, even-aged and uniform spruce forests are affected by recurring droughts and associated biotic stressors leading to large-scale diebacks across Central Europe causing controversies among foresters and nature conservationists. We investigate the role of spruce in historical woodlands by using 15666 spruce timbers from historical buildings and on the basis of pollen-based land cover estimates using the REVEALS model from 157 pollen sites in southern Central Europe. Start and end dates of the spruce timber samples and their dendrological characteristics (age, growth rates and stem diameters) were used to obtain information on past forest structures. Tree rings and REVEALS estimates are combined at a spatial scale of 1° × 1° resolution, grouped in four sub-regions, and a temporal resolution of 100-year time windows starting from 1150 to 1850 CE. We found that spruce dominates the species assemblage of construction timber with almost 41% and that the harvest age varies little through time, whereas a declining trend in growth rates and stem diameters are observed toward times before modern forestry. Temporal and regional differences in spruce abundance and building activity were found highlighting periods of (i) land abandonment and forest expansion in the 14th century, (ii) increased wood consumption during the 16th century due to population increase and beginning industrial developments, (iii) a forest recovery during and after the Thirty years' war, and (iv) afforestation efforts from the 1650s onwards. Furthermore, this study shows that spruce was constantly present in the study area in most studied sub-regions for the last 800 years. We demonstrate the need of combining tree-ring and pollen data to identify spatiotemporal patterns in spruce abundance and utilization.publishedVersio

Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes

DNA oligonucleotides (ODN) applied to an organism are known to modulate the innate and adaptive immune system. Previous studies showed that a CpG-containing ODN (CpG-1-PTO) and interestingly, also a non-CpG-containing ODN (nCpG-5-PTO) suppress inflammatory markers in skin. In the present study it was investigated whether these molecules also influence cell apoptosis. Here we show that CpG-1-PTO, nCpG-5-PTO, and also natural DNA suppress the phosphorylation of PKB/Akt in a cell-type-specific manner. Interestingly, only epithelial cells of the skin (normal human keratinocytes, HaCaT and A-431) show a suppression of PKB/Akt. This suppressive effect depends from ODN lengths, sequence and backbone. Moreover, it was found that TGFα-induced levels of PKB/Akt and EGFR were suppressed by the ODN tested. We hypothesize that this suppression might facilitate programmed cell death. By testing this hypothesis we found an increase of apoptosis markers (caspase 3/7, 8, 9, cytosolic cytochrome c, histone associated DNA fragments, apoptotic bodies) when cells were treated with ODN in combination with low doses of staurosporin, a well-known pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells

Extracellular invertase is involved in the regulation of clubroot disease in Arabidopsis thaliana

Clubroot disease of Brassicaceae is caused by an obligatebiotrophic protist,Plasmodiophora brassicae. During root galldevelopment, a strong sink for assimilates is developed. Amongother genes involved in sucrose and starch synthesis and degra-dation, the increased expression of invertases has been observedin a microarray experiment, and invertase and invertase inhibitorexpression was confirmed using promoter::GUS lines ofArabi-dopsis thaliana. A functional approach demonstrates that inver-tases are important for gall development. Different transgeniclines expressing an invertase inhibitor under the control of tworoot-specific promoters,Pyk10andCrypticT80, which results inthe reduction of invertase activity, showed clearly reduced clu-broot symptoms in root tissue with highest promoter expression,whereas hypocotyl galls developed normally. These resultspresent the first evidence that invertases are important factorsduring gall development, most probably in supplying sugars tothe pathogen. In addition, root-specific repression of invertaseactivity could be used as a tool to reduce clubroot symptoms

Cluster of human Puumala orthohantavirus infections due to indoor exposure?—An interdisciplinary outbreak investigation

Puumala orthohantavirus (PUUV) is the most important hantavirus species in Europe, causing the majority of human hantavirus disease cases. In central and western Europe, the occurrence of human infections is mainly driven by bank vole population dynamics influenced by beech mast. In Germany, hantavirus epidemic years are observed in 2- to 5-year intervals. Many of the human infections are recorded in summer and early autumn, coinciding with peaks in bank vole populations. Here, we describe a molecular epidemiological investigation in a small company with eight employees of whom five contracted hantavirus infections in late 2017. Standardized interviews with employees were conducted to assess the circumstances under which the disease cluster occurred, how the employees were exposed and which counteractive measures were taken. Initially, two employees were admitted to hospital and serologically diagnosed with hantavirus infection. Subsequently, further investigations were conducted. By means of a self-administered questionnaire, three additional symptomatic cases could be identified. The hospital patients' sera were investigated and revealed in one patient a partial PUUV L segment sequence, which was identical to PUUV sequences from several bank voles collected in close proximity to company buildings. This investigation highlights the importance of a One Health approach that combines efforts from human and veterinary medicine, ecology and public health to reveal the origin of hantavirus disease clusters.Peer Reviewe

The 12,460-Year Hohenheim Oak and Pine Tree-Ring Chronology from Central Europe—A Unique Annual Record for Radiocarbon Calibration and Paleoenvironment Reconstructions

ABSTRACT. The combined oak and pine tree-ring chronologies of Hohenheim University are the backbone of the Holocene radiocarbon calibration for central Europe. Here, we present the revised Holocene oak chronology (HOC) and the Preboreal pine chronology (PPC) with respect to revisions, critical links, and extensions. Since 1998, the HOC has been strengthened by new trees starting at 10,429 BP (8480 BC). Oaks affected by cockchafer have been identified and discarded from the chro-nology. The formerly floating PPC has been cross-matched dendrochronologically to the absolutely dated oak chronology, which revealed a difference of only 8 yr to the published 14C wiggle-match position used for IntCal98. The 2 parts of the PPC, which were linked tentatively at 11,250 BP, have been revised and strengthened by new trees, which enabled us to link both parts of the PPC dendrochronologically. Including the 8-yr shift of the oak-pine link, the older part of the PPC (pre-11,250 BP) needs to be shifted 70 yr to older ages with respect to the published data (Spurk 1998). The southern German part of the PPC now covers 2103 yr from 11,993–9891 BP (10,044–7942 BC). In addition, the PPC was extended significantly by new pine chronologies from other regions. A pine chronology from Avenches and Zürich, Switzerland, and another from the Younger Dryas forest of Cottbus, eastern Germany, could be crossdated and dendrochronologically matched to the PPC. The abso-lutely dated tree-ring chronology now extends back to 12,410 cal BP (10,461 BC). Therefore, the tree-ring-based 14C calibra-tion now reaches back into the Central Younger Dryas. With respect to the Younger Dryas-Preboreal transition identified in the ring width of our pines at 11,590 BP, the absolute tree-ring chronology now covers the entire Holocene and 820 yr of th

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029