Introducing zanadio: A digitalized, multimodal program to treat obesity

While the prevalence of overweight and obesity has been increasing annually, the accessibility of on-site treatment programs is not rising correspondingly. Digital, evidence-based obesity treatment programs could potentially alleviate this situation. The application zanadio has been developed to enable patients with obesity (BMI 30-45 kg/m2) to participate in a digital, multimodal weight reduction program based on current treatment guidelines. This article is divided into two parts: (I) it introduces zanadio, its aims and therapeutic concept, and (II) provides a first impression and demographic data on more than 11,000 patients from across the country who have used zanadio within the last 16 months, which demonstrates the demand for a digital obesity treatment. zanadio has the potential to partially close the current gap in obesity care. Future work should focus on identifying predictors of successful weight loss to further individualize digital obesity treatment, and an important next step would be to prevent obesity, i.e., to start the treatment at lower BMI levels, and to invent digital treatment programs for children and adolescents

Development of Non-Natural Flavanones as Antimicrobial Agents

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non-natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 µg/mL in E. coli when combined with the inhibitor Phe-Arg-ß-naphthylamide, and MICs of 30 µg/mL in S. cerevesiae and 30 µg/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells

The First Illumina-Based De Novo Transcriptome Sequencing and Analysis of Safflower Flowers

BACKGROUND: The safflower, Carthamus tinctorius L., is a worldwide oil crop, and its flowers, which have a high flavonoid content, are an important medicinal resource against cardiovascular disease in traditional medicine. Because the safflower has a large and complex genome, the development of its genomic resources has been delayed. Second-generation Illumina sequencing is now an efficient route for generating an enormous volume of sequences that can represent a large number of genes and their expression levels. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the genes and pathways that might control flavonoids and other secondary metabolites in the safflower, we used Illumina sequencing to perform a de novo assembly of the safflower tubular flower tissue transcriptome. We obtained a total of 4.69 Gb in clean nucleotides comprising 52,119,104 clean sequencing reads, 195,320 contigs, and 120,778 unigenes. Based on similarity searches with known proteins, we annotated 70,342 of the unigenes (about 58% of the identified unigenes) with cut-off E-values of 10(-5). In total, 21,943 of the safflower unigenes were found to have COG classifications, and BLAST2GO assigned 26,332 of the unigenes to 1,754 GO term annotations. In addition, we assigned 30,203 of the unigenes to 121 KEGG pathways. When we focused on genes identified as contributing to flavonoid biosynthesis and the biosynthesis of unsaturated fatty acids, which are important pathways that control flower and seed quality, respectively, we found that these genes were fairly well conserved in the safflower genome compared to those of other plants. CONCLUSIONS/SIGNIFICANCE: Our study provides abundant genomic data for Carthamus tinctorius L. and offers comprehensive sequence resources for studying the safflower. We believe that these transcriptome datasets will serve as an important public information platform to accelerate studies of the safflower genome, and may help us define the mechanisms of flower tissue-specific and secondary metabolism in this non-model plant

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Getting to the heart of the matter: Does aberrant interoceptive processing contribute towards emotional eating?

According to estimates from Public Health England, by 2034 70% of adults are expected to be overweight or obese, therefore understanding the underpinning aetiology is a priority. Eating in response to negative affect contributes towards obesity, however, little is known about the underlying mechanisms. Evidence that visceral afferent signals contribute towards the experience of emotion is accumulating rapidly, with the emergence of new influential models of ‘active inference’. No longer viewed as a ‘bottom up’ process, new interoceptive facets based on ‘top down’ predictions have been proposed, although at present it is unclear which aspects of interoception contribute to aberrant eating behaviour and obesity. Study one examined the link between eating behaviour, body mass index and the novel interoceptive indices; interoceptive metacognitive awareness (IAw) and interoceptive prediction error (IPE), as well as the traditional measures; interoceptive accuracy (IAc) and interoceptive sensibility (IS). The dissociation between these interoceptive indices was confirmed. Emotional eaters were characterised by a heightened interoceptive signal but reduced meta-cognitive awareness of their interoceptive abilities. In addition, emotional eating correlated with IPE; effects that could not be accounted for by differences in anxiety and depression. Study two confirmed the positive association between interoceptive accuracy and emotional eating using a novel unbiased heartbeat discrimination task based on the method of constant stimuli. Results reveal new and important mechanistic insights into the processes that may underlie problematic affect regulation in overweight populations