Soil and Vegetation Drive Sesquiterpene Lactone Content and Profile in Arnica montana L. Flower Heads From Apuseni-Mountains, Romania

Arnica montana L. (AM, Asteraceae) is a perennial, herbaceous vascular plant species of commercial importance. The flower heads’ pharmacological properties are attributed mainly to sesquiterpene lactones (SLs), with phenolic acids and flavonoids also considered of relevance. The botanical drug is still partly collected in different European mountain regions. The SL content can be influenced by genetic factors and environmental conditions (altitude, temperature and rainfall). Surprisingly, the influence of the soil on SL-content have rarely been investigated. However, the soil determines the occurrence, distribution and overall fitness of AM. Equally, environmental factors are crucial determinants for the biosynthesis and fluctuations in plant secondary metabolites. Therefore, different abiotic (pH, C/N ratio, base saturation, cation exchange capacity) and biotic (species richness, vegetation cover) parameters need to be assessed as potential drivers of the variable content of AM’s secondary metabolites. Consequently, we developed an in situ experimental design aiming to cover a wide range of soil pH conditions. We detected and investigated different AM populations growing in grassland on acidic soils, on siliceous as well as calcareous geologies within the same geographical region and altitudinal belt. The total SL content and most single SL contents of the AM flower heads differed significantly between the two geologies. AM flower heads of plants growing on loam on limestone showed a significant higher total SL content than the flower heads of plants growing in siliceous grasslands. Furthermore, the SL contents were significantly correlated with geobotanical species richness and vegetation cover pointing toward an effect of species interactions on the production of SLs. Moreover, the ratios of the main SLs helenalin to dihydrohelenalin esters were significantly correlated to environmental parameters indicating that SL composition might be a function of habitat conditions. The findings of this study shed light upon the often ignored, complex interactions between environmental conditions and plant secondary metabolites. We highlight the importance of both abiotic and biotic habitat parameters for SLs in AM

Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial

A list of investigators of the International Salofalk OD Study Group is given in the appendix. Investigators from Latvia are: Jelena Derova, Aleksejs Derovs, Juris Pokrotnieks, Aldis Pukitis, Mairita Ergle.Objectives: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. Design: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III noninferiority study. Setting: 54 centres in 13 countries. Patients: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index ≥ 4 at baseline) were randomised and treated. Interventions: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. Main outcome measures: Clinical remission (CAI ≤ 4) at study end. Results: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. Conclusions: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis. ClinicalTrials.gov Identifier: NCT00449722.publishersversionPeer reviewe

Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel

Purpose: Pathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants. Methods: The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants. Functional, computational, allelic, and segregation data were also obtained. Case-control statistical analyses were performed. Results: The panel reviewed the synthesized information, and classified the p.Met34Thr and p.Val37Ile variants utilizing professional variant interpretation guidelines and professional judgment. We found that p.Met34Thr and p.Val37Ile are significantly overrepresented in hearing loss patients, compared with population controls. Individuals homozygous or compound heterozygous for p.Met34Thr or p.Val37Ile typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for these two variants. Conclusion: Resolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification guidelines, review evidence, and reach a consensus. We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. METHODS: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. RESULTS: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. CONCLUSIONS: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029

deadtrees.earth — An open-access and interactive database for centimeter-scale aerial imagery to uncover global tree mortality dynamics

Excessive tree mortality is a global concern and remains poorly understood as it is a complex phenomenon. We lack global and temporally continuous coverage on tree mortality data. Ground-based observations on tree mortality, e.g., derived from national inventories, are very sparse, and may not be standardized or spatially explicit. Earth observation data, combined with supervised machine learning, offer a promising approach to map overstory tree mortality in a consistent manner over space and time. However, global-scale machine learning requires broad training data covering a wide range of environmental settings and forest types. Low altitude observation platforms (e.g., drones or airplanes) provide a cost-effective source of training data by capturing high-resolution orthophotos of overstory tree mortality events at centimeter-scale resolution. Here, we introduce deadtrees.earth, an open-access platform hosting more than two thousand centimeter-resolution orthophotos, covering more than 1,000,000 ha, of which more than 58,000 ha are manually annotated with live/dead tree classifications. This community-sourced and rigorously curated dataset can serve as a comprehensive reference dataset to uncover tree mortality patterns from local to global scales using space-based Earth observation data and machine learning models. This will provide the basis to attribute tree mortality patterns to environmental changes or project tree mortality dynamics to the future. The open nature of deadtrees.earth, together with its curation of high-quality, spatially representative, and ecologically diverse data will continuously increase our capacity to uncover and understand tree mortality dynamics

Taxonomic significance of alkaloids in the genus Liparia (Fabaceae – Liparieae)

Comparative GC and GC–MS analyses of the alkaloids of Liparia splendens (Burm. f.) Bos & De Wit and L. parva Vog. ex Walp. have shown that the two species differ considerably. L. splendens contains ammodendrine (a bipiperidyl compound) as major alkaloid, while L. parva has sparteine, lupanine and other quinolizidine alkaloids as major alkaloids. Only small quantities of bipiperidyl alkaloids were present in the latter. The two species of Liparia are morphologically similar and the different alkaloid patterns are therefore quite unexpected. Our results support the idea that different pollination mechanisms may lead to an enlarged taxonomic distance between closely related species

The major alkaloids of the genus Polhillia

The major alkaloids of three species of Polhillia Stirton and three species of Argyrolobium Eckl. & Zeyh. have been identified. The presence of sparteine, lupanine, anagyrine and N-methylcytisine as major alkaloids in Polhillia and in the morphologically similar Argyrolobium brevicalyx Stirton indicates a direct phylogenetic link between Polhillia (Crotalarieae) and Argyrolobium (Genisteae). The data also supports the transfer of Melolobium involucratum (Thunb.) Stirton to Polhillia