Gold Nanoparticles‐Titania Heterojunction: Photoelectrochemical Detection of Ciprofloxacin

A photoelectrochemical sensor composed of a heterojunction between titanium dioxide and gold nanoparticles was fabricated and used for the determination of ciprofloxacin, a widely used, but environmentally toxic third-generation antibiotic. This material has been extensively characterized from the morphological, electrochemical and photoelectrochemical points of view, comparing it with the respective counterparts. It has been demonstrated that only the presence of the heterojunction allows the detection of ciprofloxacin, thanks to the properties of gold nanoparticles combined with those of titanium dioxide. These increased performances have allowed the detection of the analyte even with low power sources and wavelengths in the visible region, obtaining good detection limits and excellent resistance to possible interferents. Thanks to this, the future implementation of these sensors in integrated circuits for online and onsite analysis is foreseen

Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib

Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib, to clarify the interpatient variability in exposure. In addition, this study explores the relationship between target receptor polymorphisms and toxicity of danusertib. Methods For associations with clearance, 48 cancer patients treated in a phase I study were analyzed for ABCB1, ABCG2 and FMO3 polymorphisms. Association analyses between neutropenia and drug target receptors, including KDR, RET, FLT3, FLT4, AURKB and AURKA, were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials. Results No relationships between danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found. Only, for the one patient with FMO3 18281AA polymorphism, a significantly higher clearance was noticed, compared to patients carrying at least 1 wild type allele. No effect of target receptor genotypes or haplotypes on neutropenia was observed. Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients

Characterization and Management of Stable Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background/Objectives: To date, data regarding the characteristics and management of obstructive, stable coronary artery disease (CAD) encountered in patients undergoing transcatheter aortic valve implantation (TAVI) are sparse. The aim of the study was to analyze granular details, treatment, and outcomes of patients undergoing TAVI with obstructive, stable CAD from real-world practice. Methods: REVASC-TAVI (Management of myocardial REVASCularization in patients undergoing Transcatheter Aortic Valve Implantation with coronary artery disease) is an investigator-initiated, multicenter registry, which collected data from patients undergoing TAVI with obstructive stable CAD found during the pre-TAVI work-up. Results: A total of 2025 patients from 30 centers worldwide with complete follow-up were included in the registry. Most patients had single-vessel CAD (56.1%). An involvement of proximal coronary tracts was detected in 62.5% of cases, with 12.0% of patients having CAD in left main (LM). Most patients received percutaneous coronary intervention (PCI) (n = 1617, 79.9%), especially those with proximal CAD (90.4%). At 2 years, the rates of all-cause death [Kaplan-Meier (KM) estimates 20.1% vs. 18.8%, plog-rank = 0.86] and of the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure (KM estimates 29.7% vs. 27.5%, plog-rank = 0.82) did not differ between patients undergoing PCI and those who were not. Conclusions: Patients undergoing TAVI with obstructive CAD more commonly had a single-vessel disease and an involvement of proximal coronary tracts. They were commonly treated with PCI, with similar outcomes compared to those treated conservatively

TOSCA – first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex

Abstract Background Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies. Methods TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a ‘core’ section and subsections or ‘petals’. The ‘core’ section is designed to record general information on patients’ background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24 months. A follow-up observation period of up to 5 years is planned. Results A pre-planned administrative analysis of ‘core’ data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to data availability in 2014. Implications The results of TOSCA will assist in filling the gaps in understanding the natural history of TSC and help in planning better management and surveillance strategies. This large-scale international registry to study TSC could serve as a model to encourage planning of similar registries for other rare diseases

Environmental photodegradation of emerging contaminants: A re-examination of the importance of triplet-sensitised processes, based on the use of 4-carboxybenzophenone as proxy for the chromophoric dissolved organic matter

International audienceThe photoreactions sensitised by the excited triplet states of chromophoric dissolved organic matter (3CDOM*) are very important in the photochemical attenuation of emerging contaminants in natural waters. Until quite recently, anthraquinone-2-sulphonate (AQ2S) was the only available CDOM proxy molecule to estimate the contaminant reaction kinetics with 3CDOM*, under steady-state irradiation conditions. Unfortunately, the AQ2S triplet state (3AQ2S*) is considerably more reactive than average 3CDOM*. We have recently developed an alternative protocol based on 4-carboxybenzophenone (CBBP), the triplet state of which (3CBBP*) is less reactive compared to 3AQ2S*. Here we show that in the case of ibuprofen (IBP), paracetamol (APAP) and clofibric acid (CLO), the reaction rate constants with 3CBBP* are more reasonable as 3CDOM* reactivity estimates than those obtained by using AQ2S. In contrast, similar rate constants are measured for the reaction of atrazine (ATZ) with either 3AQ2S* or 3CBBP*. Moreover, the reactivity of ATZ with both 3AQ2S* and 3CBBP* is very similar to that with 3CDOM*, available through a literature estimate. The possibility to validate the ATZ-3CBBP* reactivity estimate against the 3CDOM* data, and to accurately predict the reported IBP and CLO field lifetime, support the suitability of CBBP as CDOM proxy. The replacement of AQ2S with CBBP as proxy molecule does not reverse the qualitative prediction, according to which 3CDOM* would be the main process involved in the photodegradation of the studied contaminants in waters with high dissolved organic carbon (DOC). However, the CBBP-based data prompt for an important reconsideration of the estimated lifetimes at high DOC

PSICOLOGIA E POLÍTICAS PÚBLICAS: CAMINHOS E PERSPECTIVAS PARA UMA PRÁXIS PSICOLÓGICA NO ATRAVESSAMENTO DA CRISE SANITÁRIA

Em detrimento da crise sanitária causada pela pandemia de covid-19 em 2020, surge a inquietação para entender como os desdobramentos de um problema de saúde global é percebido pelos profissionais psicólogos atuantes nas políticas públicas de saúde. Para responder a tal inquietação desenvolveu-se uma pesquisa qualitativa a partir de entrevistas semiestruturadas com 6 psicólogas atuantes em equipamentos públicos de saúde (CAPS ad, Consultório na Rua, UBS e Hospital Geral), cujo dados coletados foram analisados através da análise temática de conteúdo. Fora possível obter como resultados, a dimensão de que a crise sanitária é compreendida com baseada nas consequências e afetações que ocorreram na estrutura social e a necessidade de se voltar para as teorias da Psicologia existentes que dão conta de olhar para os fenômenos de maneira macro, no campo das intersubjetividades, como é o caso da Psicologia Social, gerando possibilidades de oferecer aos sujeitos a construção de recursos de enfrentamento ao contexto de pandemia bem como às questões que a precedem e continuam a existir durante a pandemia, sendo agravadas ou não por ela.</jats:p

A retrospective analysis of CDK4/6 inhibitors among adult female patients with metastatic breast cancer.

e13028 Background: The aim of this study is to examine the behavior pattern of cyclin-dependent kinase (CDK4/6) inhibitor combinations in adult females with de novo metastatic breast cancer as first therapy or following adjuvant hormonal therapy. Methods: Using United States open health claims and prescription data we analyzed metastatic breast cancer from 2015 Q1 to 2019 Q4, adult female patients (age ≥18). Patients were classified into 3 groups based on their first therapy: Group 1-Hormonal, Group 2-CDK4/6 Inhibitor Combinations, and Group 3-Everolimus Combination. Analysis was completed using the Chi-Squared goodness of fit test assessing the patients moving to next therapy by time period. We also compared the overall CDK4/6 group as a base for probability distribution to study the pattern of therapy change in individual groups. Results: Of 37,351 patients on CDK4/6 inhibitors as first therapy or following adjuvant hormonal therapy for advanced/metastatic diseases, the percentage of patients who moved to next therapy was 3.2% (1,200 patients). For most patients, change in therapy occurred within a 2-year period (87%) and those who remained on their first therapy continued for an extended duration. In both Groups 1 and 2 no statistically significant difference was found in the treatment pattern compared to the overall CDK4/6 inhibitor patient population. However, most patients in Group 3 (90%) compared to the overall patient population on CDK4/6 inhibitors moved to Chemotherapy within the first year of treatment (statistically significant at p-value = 0.02). Further analysis of granularity in individual patient pathways showed about 90% of patients with CDK4/6 inhibitors remained on therapy for about 1 year and, interestingly, about 2% extended beyond 2 years up to 4.5 years. Conclusions: The results show most patients on CDK4/6 inhibitors (95%) had progression free survival (PFS) for the period we analyzed. Overall, patients on CDK4/6 inhibitors behaved similarly when used as first therapy or following adjuvant hormonal therapy. </jats:p

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

Contains fulltext : 126057.pdf (preprint version ) (Open Access