A New Biocatalyst for Production of Optically Pure Aryl Epoxides by Styrene Monooxygenase from Pseudomonas fluorescens ST

We developed a biocatalyst by cloning the styrene monooxygenase genes (styA and styB) from Pseudomonas fluorescens ST responsible for the oxidation of styrene to its corresponding epoxide. Recombinant Escherichia coli was able to oxidize different aryl vinyl and aryl ethenyl compounds to their corresponding optically pure epoxides. The results of bioconversions indicate the broad substrate preference of styrene monooxygenase and its potential for the production of several fine chemicals

Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma

Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution. ULP-WGS of these patients proved effective in revealing the marked genome-wide level of their CNAs, most of which are not routinely investigated. Finally, the analysis of our small SMM cohort suggested that chr(8p) deletions, the DNA tumor fraction, and the number of alterations may have clinical relevance in the progression to overt MM. Although validation in larger series is mandatory, these findings highlight the promising impact of genomic approaches in the clinical management of SMM

COVID-19 as a Paradigmatic Model of the Heterogeneous Disease Presentation in Older People: Data from the GeroCovid Observational Study

COVID-19 may have a heterogeneous onset, especially in older age. However, whether and how COVID-19 signs and symptoms may present and aggregate together according to sociodemographic and health factors is unclear, as well as their prognostic value. This study included 981 COVID-19 inpatients who participated in the GeroCovid Observational study. Signs/symptoms at disease onset, sociodemographic, health, cognitive status, and mobility were systematically recorded. Clusters of signs/symptoms were identified through agglomerative hierarchical clustering. The associations of single signs/symptoms and symptom clusters with longer hospitalization (>= 16 days) and in-hospital mortality were explored through logistic and Cox regressions. The signs/symptoms most reported in our sample (age 78.3 +/- 9.39 years; 49.4% women) were fever (62.5%), cough (45.5%), and dyspnea (62.7%). Atypical symptoms were reported by up to one-third of patients, and delirium by 9.1%. Atypical symptoms were more frequent with advancing age and with lower pre-COVID-19 cognitive and mobility levels. Older men more likely reported respiratory symptoms than women. Dyspnea (hazard ratio [HR] = 1.47, 95% confidence interval [CI]: 1.02-2.12), tachypnea (HR = 1.53, 95% CI: 1.14-2.07), low oxygen saturation (HR = 1.95, 95% CI: 1.32-2.88) and delirium (HR = 1.60, 95% CI: 1.13-2.28) were associated with higher in-hospital mortality. Four symptom clusters were identified. Compared with the mild respiratory symptoms cluster, the severe clinical impairment cluster was associated with higher mortality (HR = 2.57, 95% CI: 1.58-4.18). The severe clinical impairment and aspecific symptoms clusters were associated with longer hospitalization (odds ratio [OR] = 2.38, 95% CI: 1.56-3.63, and OR = 1.75, 95% CI: 1.08-2.83, respectively). Multiple health aspects influence COVID-19 clinical presentation. A symptom clusters approach may help predict adverse health outcomes in older patients. In addition to respiratory symptoms, delirium is independently associated with mortality risk.ClinicalTrials.gov (NCT04379440)