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The article discusses that the war in Ukraine has been fought with the conventional and economic weapon of diverse mechanisms of economic and financial coercion. The language of economic coercion and submission highlights the connection between sanctions and other forms of economic pressure that are central to the operation of the world economy, from debt conditionality to the silent compulsion of economic relations.

Objective: Generalized anxiety disorder (GAD) is a debilitating condition, characterized by negative interpretations about ambiguous situations. This study tested whether entirely internet-delivered interpretation training [cognitive bias modification (CBM)] versus control promotes positive interpretations and reduces worry and anxiety in individuals with GAD, with or without depression. Method: A two-arm (CBM; control) parallel-group randomized controlled experiment. Assessments were preintervention (T0), postintervention (T1), 1-month (T2) postintervention, and 3-month (T3) postintervention. Participants with GAD (with or without comorbid depression) were randomly allocated to either CBM (n = 115) or control (n = 115). Participants, but not researchers, were blind to allocated condition. Participants completed up to 10 online CBM or control sessions across 1 month. Interpretation bias [coprimary outcomes: scrambled sentence test (SST), recognition test (RT)], and number of negative thought intrusions during a breathing focus task were measured at T0 and T1. Self-reported levels of worry [Penn State Worry Questionnaire-trait (PSWQ trait); Penn State Worry Questionnaire-past week (PSWQ weekly)], anxiety [Generalized Anxiety Disorder scale (GAD-7)], depression [Patient Health Questionnaire (PHQ-9)], rumination [Ruminative Response Scale (RRS)], and repetitive negative thinking [RNT; Repetitive Thinking Questionnaire-trait (RTQ-trait)] were assessed at T0–T3. Results: The per-protocol analyses included N = 186 participants (CBM n = 94; control n = 92). As predicted, we found moderate-to-large training effects on the primary outcome of interpretation bias at T1. Secondary outcomes of negative thought intrusions at T1 and self-reported symptoms at T2 were all significantly lower in the CBM versus control condition. All but one effect (trait RNT) were sustained at T3. Conclusions: In this randomized controlled study, we found that fully online interpretation training ameliorated core features of GAD in individuals with or without comorbid depression up to 3 months posttraining. What is the public health significance of this article?: Generalized anxiety disorder (GAD) is a common debilitating problem with uncontrollable worry at its core. It often co-occurs with clinical depression. The tendency to draw negative conclusions from unclear/ambiguous information (interpretation bias) maintains worry, anxiety, and depression. This web-based study of people with GAD (with or without depression) used computerized practice in generating positive interpretations and compared this training to another (control) condition which did not alter interpretations. Positive interpretation training reduced worry, anxiety, and depression up to 3 months after training finished. The effects were due to changes in interpretation bias. Given the online nature of the interpretation training, this indicates for the first time that interpretation training can be effective when delivered remotely to people suffering from GAD with or without depression, opening up the possibility that this approach could be used to help people recover from anxiety and depression without attending a clinic. [ABSTRACT FROM AUTHOR]

The fungal pathogen Cryptococcus neoformans is a leading cause of meningoencephalitis in the immunocompromised. As current antifungal treatments are toxic to the host, costly, limited in their efficacy, and associated with drug resistance, there is an urgent need to identify vulnerabilities in fungal physiology to accelerate antifungal discovery efforts. Rational drug design was pioneered in de novo purine biosynthesis as the end products of the pathway, ATP and GTP, are essential for replication, transcription, and energy metabolism, and the same rationale applies when considering the pathway as an antifungal target. Here, we describe the identification and characterization of C. neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/5'-inosine monophosphate cyclohydrolase (ATIC), a bifunctional enzyme that catalyzes the final two enzymatic steps in the formation of the first purine base inosine monophosphate. We demonstrate that mutants lacking the ATIC-encoding ADE16 gene are adenine and histidine auxotrophs that are unable to establish an infection in a murine model of virulence. In addition, our assays employing recombinantly expressed and purified C. neoformans ATIC enzyme revealed Km values for its substrates AICAR and 5-formyl-AICAR are 8-fold and 20-fold higher, respectively, than in the human ortholog. Subsequently, we performed crystallographic studies that enabled the determination of the first fungal ATIC protein structure, revealing a key serine-to-tyrosine substitution in the active site, which has the potential to assist the design of fungus-specific inhibitors. Overall, our results validate ATIC as a promising antifungal drug target. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is an inflammatory disease leading to spine ankylosis; however, the mechanisms behind new bone formation are still not fully understood. Single Nucleotide Polymorphisms (SNPs) in PTGER4, encoding for the receptor EP4 of prostaglandin E2 (PGE2), are associated with AS. Since the PGE2-EP4 axis participates in inflammation and bone metabolism, this work aims at investigating the influence of the prostaglandin-E2 axis on radiographic progression in AS. In 185 AS (97 progressors), baseline serum PGE2 predicted progression, and PTGER4 SNP rs6896969 was more frequent in progressors. Increased EP4/PTGER4 expression was observed in AS circulating immune cells, synovial tissue, and bone marrow. CD14highEP4 + cells frequency correlated with disease activity, and when monocytes were cocultured with mesenchymal stem cells, the PGE2/EP4 axis induced bone formation. In conclusion, the Prostaglandin E2 axis is involved in bone remodelling and may contribute to the radiographic progression in AS due to genetic and environmental upregulation. • PGE2 serum level predicts radiographic progression in Ankylosing Spondylitis. • EP4 is upregulated in AS by genetic and environmental factors. • PGE2/EP4 axis is upregulated in AS in synovial tissue, bone marrow and peripheral blood. • EP4+ circulating monocytes are increased in AS and correlated with disease activity and smoking. • PGE2/EP4 axis modulated monocyte-induced bone formation in MSCs. [ABSTRACT FROM AUTHOR]