Presence of Destruxin A and Beauvericin in cereals

A LC-MS/MS method for the detection of destruxin A (DTX A) and beauvericin (BEA) in cereals was developed, validated and applied to commercial products collected in Italian markets in the years 2015-2016. Results showed that BEA contaminated 59 % of the samples even if only 15 of them (34%) showed quantifiable residues (comprised between 0.11 and 7.51 ng/g). The sample of red rice contaminated with the highest BEA level was also contaminated with DTX A (0.28 ng/g). Finally, no significant differences were detected between contaminated samples based on the production year and the agronomic technology used (organic or conventional farming)

Strategies for management of strongyloidiasis in migrants from Sub-Saharan Africa recently arrived in Italy: A cost-effectiveness analysis

Abstract Background The Italian and the European Centre for Disease Control and Prevention guidelines both recommend a systematic serological screening for strongyloidiasis in sub-Saharan migrants (SSA), however, studies on clinical and economic impact of this strategy in the Italian and European settings are lacking. Methods A population of 100,000 migrants from SSA to Italy was considered and a Markov decision tree model was developed to assess the clinical and economic impact of two interventions for strongyloidiasis compared with the current practice (passive diagnosis of symptomatic cases): a) universal serological screening and treatment with ivermectin in case of positive test b) universal presumptive treatment with ivermectin. One and 10-year time horizon in the health-care perspective were considered. Results In the one and 10-year time horizon respectively the costs for passive diagnosis was €1,164,169 and €9,735,908, those for screening option was € 2,856,011 and € 4,959,638 and those for presumptive treatment was €3,538,474 and € 4,883,272. Considering the cost per cured subject in the one-year time horizon, screening appears more favorable (€209.53), than the other two options (€232.55 per presumptive treatment and €10,197.29 per current strategy). Incremental cost-effectiveness ratio (ICERs) of screening strategy and presumptive treatment were respectively 265.27 and 333.19. The sensitivity analysis identified strongyloidiasis' prevalence as the main driver of ICER. Conclusions Compared to the current practice (passive diagnosis) both screening and presumptive treatment strategies are more favorable from a cost-effectiveness point of view, with a slight advantage of the screening strategy in a one-year time horizon

Disseminated and Relapsing Cryptococcosis: What We Still Have to Learn—a Case Series and Review of Literature

AbstractTwo cases of disseminated cryptococcosis are described. The first was an HIV-infected patient where cryptococcosis was diagnosed as "unmasking immune reconstitution syndrome"; the second was an immunosuppressed patient with multiple myeloma. In both cases, a definitive healing could not be reached despite long therapeutic approaches. This review summarizes both the most recent and relevant studies about disseminated and refractory form of cryptococcal infections and identifies research gaps. Given the limited data, we draw some conclusions with respect to management from literature: not clear and accepted indication are available regarding disseminated cryptococcosis, no specific schemes were identified, and the duration of therapy is usually decided case by case and supported only by case reports. In this perspective, usually standard therapeutic schemes and duration of induction depend on multiple factors (e.g., neurologic deficit, non-HIV/non transplant status, CSF culture positivity at 2 weeks, etc.). We found that there are no empiric and literature data that support a role of cryptococcal serum antigen (CRAG) in guiding the antifungal therapy; with the data collected, we think that although is possible, it is very rare to find disseminated cryptococcosis with negative CRAG. We looked also for the more important risk factor of recurrence. Some possible causes explored are risk of azole resistant strains, pre-existent conditions of patients that play a permissive role and the common situation where flucytosine is unavailable that led to suboptimal induction phase of therapy. Herein, we discuss disseminated cryptococcosis with a particular attention to antifungal therapy, role of cryptococcal antigen, and risk factors for recurrence of disease

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

LINSEED TO INCREASE N-3 FATTY ACIDS IN TENEBRIO MOLITOR (COLEOPTERA TENEBRIONIDAE)

The yellow mealworm Tenebrio molitor is one of the most promising edible insect species for human consumption and its potential use as a supplement of unsaturated fatty acids (UFA) for human diet, has been recently confirmed. The possibility to enhance polyunsaturated acids (PUFA), especially omega-3 (n-3) content, was evaluated in T. molitor mealworms. The purpose was to obtain an n-6/n-3 ratio more suitable for human consumption, which is useful for the secondary prevention of cardiovascular diseases. To this end, tests were carried out by adding linseed, as source of n-3 acid, to insect feeding diets. A decrease of saturated fatty acids (SFA) and an increase of PUFA contents, especially n-3 acid, was simultaneously observed in larvae fed on almost all the diets enriched with linseed. As a result, supplementation of feeding diets with linseed determined a favorable insect growth rate and a decrease of n-6/n-3 ratio to values more suitable for the prevention and treatment of cardiovascular diseases

Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions

Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan parasite <i>Giardia duodenalis</i>, which affects annually over 200 million people worldwide. The limited antigiardial drug arsenal and the emergence of clinical cases refractory to standard treatments dictate the need for new chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively involved in protein–protein interactions (PPIs) with pSer/pThr clients, represents a highly promising target. Despite homology with human counterparts, the single 14-3-3 of <i>G. duodenalis</i> (g14-3-3) is characterized by a constitutive phosphorylation in a region critical for target binding, thus affecting the function and the conformation of g14-3-3/clients interaction. However, to approach the design of specific small molecule modulators of g14-3-3 PPIs, structural elucidations are required. Here, we present a detailed computational and crystallographic study exploring the implications of g14-3-3 phosphorylation on protein structure and target binding. Self-Guided Langevin Dynamics and classical molecular dynamics simulations show that phosphorylation affects locally and globally g14-3-3 conformation, inducing a structural rearrangement more suitable for target binding. Profitable features for g14-3-3/clients interaction were highlighted using a hydrophobicity-based descriptor to characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in complex with a mode-1 prototype phosphopeptide was solved and combined with structure-based simulations to identify molecular features relevant for clients binding to g14-3-3. The data presented herein provide a further and structural understanding of g14-3-3 features and set the basis for drug design studies

THE POTENTIAL BENEFICIAL EFFECTS OF TENEBRIO MOLITOR (COLEOPTERA TENEBRIONIDAE) AND GALLERIA MELLONELLA (LEPIDOPTERA PYRALIDAE) ON HUMAN HEALTH

The nutritional composition of the edible insect species Tenebrio molitor (Coleoptera: Tenebrionidae) and Galleria mellonella (Lepidoptera: Pyralidae) was evaluated in view of their feasible consumption in human diet. Larvae and pupae of both the edible insect species resulted to be a good energy source because of their high total fat content (37.42-48.97% of dry weight). Fatty acid composition was similar in T. molitor larvae and pupae. Conversely, G. mellonella larvae contained a higher percentage of medium and long-chain saturated fatty acids (SFA) than pupae (p= 0.015) while G. mellonella pupae showed a higher content of polyunsaturated fatty acids (PUFA) and a lower n-6/n-3 ratio than larvae (p= 0.003 and p= 0.006, respectively). Both the species contained low cholesterol values (13.56-29.08 mg/100 g of dry weight). The ability of the protein extracts from these insects to reduce blood pressure by inhibiting angiotensin converting enzyme (ACE) has been also investigated. Significantly lower IC50 values were detected either in T. molitor (0.077-0.097 mg/mL) or G. mellonella (0.046-0.605 mg/mL) protein fractions hydrolyzed by gastrointestinal proteases than the corresponding crude extracts. Even if the mealworm T. molitor and the waxmoth G. mellonella show satisfactory values of UFA, low cholesterol contents and the ability to inhibit ACE in vitro, T. molitor larvae provide the SFA/UFA ratio (0.41) that better meets diet requirements for human health, as well as a high environmental efficiency of production. These results suggest the potential use of T. molitor larvae in food industry as ingredient in fortified foods and/or diet supplements for human consumption

Efficacy and Safety of Vernakalant in Recent-Onset Atrial Fibrillation After the European Medicines Agency Approval: Systematic Review and Meta-Analysis

Vernakalant is an emergent antiarrhythmic drug that, in preclinical studies, has demonstrated high efficacy in restoring sinus rhythm and safety in patients with rapid recent-onset atrial fibrillation. The aim of this work was to evaluate the efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation. PubMed, EMBASE, Clinical Trials Registry, and European Medicines Agency public reports were searched for randomized clinical trials, until May 2011, of vernakalant compared with controls (placebo/other antiarrhythmic drug) in enrolled patients with high ventricular rate atrial fibrillation. Five randomized trials that met inclusion criteria enrolled a total of 1099 patients. Among these, 810 had recent-onset atrial fibrillation. When compared with controls (placebo/other oral antiarrhythmic drugs), vernakalant was associated with a significant increase in cardioversion within 90 minutes from drug infusion (relative risk, 8.4; 95% confidence interval, 4.4-16.3; P < .00001). Compared with controls, vernakalant was not associated with a significant difference in serious adverse events (relative risk, 0.9; 95% confidence interval, 0.6-1.4; P = .64). The authors conclude that compared with controls, vernakalant is effective and safe for rapidly converting recent-onset atrial fibrillation. Questions remain surrounding safety because 1 unpublished trial was discontinued for this reason. Further cost-effective analysis and comparison with other antiarrhythmic agents, such as class I antiarrhythmic agents, should be investigated, especially in the emergency department