Occupational risk prevention in hospitals based on the Cultural-Historical Activity Theory. / Prevenção de riscos e agravos à saúde dos trabalhadores hospitalares à luz da Teoria da Atividade Histórico-Cultural.

Hospital managers should target occupational risks and harm prevention since this can contribute to the quality of life at work and patient safety. This article aims to elucidate the activity of prevention of occupational risks and injuries in the hospital setting based on analysis of historical and empirical contradictions of the activity system. An exploratory qualitative study grounded in the Cultural-Historical Activity Theory was conducted at a university hospital in the state of São Paulo. Data were collected between September 2021 and January 2022 via individual semi-structured interviews of 9 professionals from the Occupational Health and Safety services and of five hospital managers, involving 20 hours of field observation and document analysis. Despite the expansion of the object of prevention activity, the other elements of the activity system did not adapt to the new demands, causing incompatibilities and contradictions that compromised the attainment of the expected outcomes. The main response actions observed were centered on complying with regulatory items, such as team composition, medical examinations and others, that contribute little toward promoting occupational health and safety.

A prevenção de riscos e agravos à saúde dos trabalhadores nos hospitais deve ser foco dos gestores, pois contribui para a qualidade de vida no trabalho e a segurança do paciente. O objetivo deste artigo é compreender a atividade de prevenção de riscos e agravos à saúde dos trabalhadores no contexto hospitalar, a partir das contradições históricas e empíricas do sistema de atividade. Estudo qualitativo exploratório, ancorado na Teoria da Atividade Histórico-Cultural, desenvolvido em um hospital universitário do estado de São Paulo. Os dados foram coletados entre setembro de 2021 e janeiro de 2022 por meio de entrevistas semiestruturadas com nove profissionais do Serviço Especializado em Engenharia de Segurança e Medicina do Trabalho e cinco gestores do hospital; 20 horas de observação de campo; e análise documental. Apesar da expansão do objeto da atividade de prevenção, os demais elementos do sistema de atividade não se adaptaram às novas exigências, evoluindo com incompatibilidades e contradições que comprometeram o alcance dos resultados esperados. As principais ações de resposta observadas ficaram centradas em adequações a exigências de itens de normas, como composição de equipe, exames médicos e outras que pouco atuam na promoção e proteção da saúde.

Easy Synthetic Access to High-Melting Sulfurated Copolymers and their Self-Assembling Diblock Copolymers from Phenylisothiocyanate and Oxetane.

Although sulfurated polymers promise unique properties, their controlled synthesis, particularly when it comes to complex and functional architectures, remains challenging. Here, we show that the copolymerization of oxetane and phenyl isothiocyanate selectively yields polythioimidocarbonates as a new class of sulfur containing polymers, with narrow molecular weight distributions (Mn=5-80 kg/mol with D≤1.2; Mn,max=124 kg/mol) and high melting points of up to 181 °C. The method tolerates different substituent patterns on both the oxetane and the isothiocyanate. Self-nucleation experiments reveal that π-stacking of phenyl substituents, the presence of unsubstituted polymer backbones, and the kinetically controlled linkage selectivity are key factors in maximising melting points. The increased tolerance to macro-chain transfer agents and the controlled propagation allows the synthesis of double crystalline and amphiphilic diblock copolymers, which can be assembled into micellar- and worm-like structures with amorphous cores in water. In contrast, crystallization driven self-assembly in ethanol gives cylindrical micelles or platelets.

Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π-π interactions.

Insufficient stability of micellar drug delivery systems is still the major limitation to their systematic application in chemotherapy. This work demonstrates novel π-electron stabilized polyelectrolyte block copolymer micelles based on dendritic polyglycerolsulfate-cystamine-block-poly(4-benzoyl-1,4-oxazepan-7-one)-pyrene (dPGS-SS-POxPPh-Py) presenting a very low critical micelle concentration (CMC) of 0.3 mg L-1 (18 nM), 55-fold lower than that of conventional amphiphilic block copolymer micelles. The drug loading capacities of up to 13 wt% allow the efficient encapsulation of the chemotherapeutic Docetaxel (DTX). The spherical morphology of the micelles was proven by cryogenic electron microscopy (cryo-EM). Gaussian Analysis revealed well-defined sizes of 57 nm and 80 nm in the unloaded/loaded state, respectively. Experiments by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), fluorescence spectroscopy, and cross-polarization solid-state 13C NMR studied the π-π interactions between the core-forming block segment of dPGS-SS-POxPPh-Py and DTX. The findings point to a substantial contribution of these noncovalent interactions to the system's high stability. By confocal laser scanning microscopy (CLSM), the cellular uptake of fluorescein-labelled FITC-dPGS-SS-POxPPh-Py micelles was monitored after one day displaying the successful cell insertion of the cargo-loaded systems. To ensure the drug release in cancerous cells, the disassembly of the micellar DTX-formulations was achieved by reductive and enzymatic degradation studied by light scattering and GPC experiments. Further, no size increase nor disassembly in the presence of human serum proteins after four days was detected. The precise in vitro drug release was also given by the high potency of inhibiting cancer cell growth, finding half-maximal inhibitory concentrations (IC50) efficiently reduced to 68 nM coming along with high viabilities of the empty polymer materials tested on tumor-derived HeLa, A549, and McF-7 cell lines after two days. This study highlights the substantial potential of micelles tailored through the combination of π-electron stabilization with dendritic polyglycerolsulfate for targeted drug delivery systems, enabling them to have a significant foothold in the clinical treatment of cancer.

Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications.

Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.

Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)-SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting.

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in light of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81-187 nm, strong negative charges between -52 and -41 mV, and low critical micelle concentrations (CMCs) of up to 1.13-3.58 mg/L (134-527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8-17 wt %). The release was selectively triggered by glutathione (GSH) and lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high cancer cell toxicity of Sunitinib-loaded micelles (IC50 2.5 µg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS7.8-SS-PCL7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG3.9-SS-PCL7.8. As a proof of concept, Sunitinib-loaded dPGS-SS-poly(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

Using a game engine for simulation in ergonomics analysis, design and education: An exploratory study.

Among the possible approaches for building virtual environments (VE), researchers have recently started employing game engines (GE). Although there are already studies reporting the usage of GE-based VEs, their potential for supporting a more comprehensive workspace analysis (considering the physical, organizational and cognitive aspects of work) has yet to be better understood. The main goal of this paper is to investigate how a GE-based simulation of a real workplace (a local control room in an oil refinery) can be used as a tool by practitioners and researchers in evaluating work conditions. Participants (n = 38) were recruited to explore the simulation and evaluate the workplace dimensions represented. A comparison between the scores participants attributed to the work dimensions and the scores assigned by the ergonomics consultant was performed through a statistical test to verify whether they significantly differed or not. Out of the 10 aspects evaluated, only 3 presented significant differences, thus showing that GE suitability for ergonomics analysis is conditioned to the aspects represented. Qualitative data analysis highlighted participants' perception of GEs potential as an analysis and educational tool, as well as a medium for fostering communication and stakeholder involvement in the design process.