Acidentes ampliados - mais do que um conceito, uma história de luta que precisa ser atualizada / Major accidents: more than a concept, a history of struggle that must be updated

Resumo Os eventos definidos como acidentes ampliados surgem com o próprio processo de industrialização, assim como junto ao desenvolvimento de novas tecnologias de produção, tornando-se mais complexos neste início de século XXI. O objetivo deste ensaio foi apresentar e contextualizar a formulação de um conceito que buscou integrar os temas relacionados à segurança e saúde dos trabalhadores com os de saúde ambiental, bem como as lutas que envolviam os trabalhadores e o processo de democratização no país, em um cenário de divisão internacional do trabalho, riscos e benefícios. Considerando os acidentes e desastres ocorridos nos anos 1980 do século XX e, também, os recentes, envolvendo barragens de mineração, derrames de petróleo e uma usina nuclear de Fukushima, são apontados cenários mais complexos e novos desafios para enfrentamento desta questão no século XXI. Para além das disfunções dos sistemas tecnológicos e organizacionais encontradas, a intensificação das vulnerabilidades institucionais, somada às vulnerabilidades produzidas pelas desigualdades sociais, potencializam ocorrências e agravam os efeitos dos acidentes, ampliados para além de suas fronteiras espaciais e temporais, afetando sobretudo países do Sul Global. Conclui-se que os eventos recentes constituem expressões sistêmicas, indo além das disfunções organizacionais e revelando camadas mais profundas de sistemas organizacionais e sociotécnicos, como as que forjam a economia global e suas profundas assimetrias.

Abstract Events defined as major accidents emerged with the very industrialization process and alongside the development of new production technologies, becoming more complex in the early 21st century. This essay aimed to describe and contextualize the formulation of a concept that has sought to integrate topics related to workers' safety and health with those of environmental health, workers' struggles, and the democratization process in Brazil in a scenario of international division of labor, risks, and benefits. Considering the accidents and disasters in the 1980s and the more recent ones involving mine tailings dams, oil spills, and the Fukushima nuclear power plant, the authors identify more complex scenarios and new challenges for tackling this issue in the 21st century. Beyond dysfunctions in technological and organizational systems, the intensification of institutional vulnerabilities, added to the vulnerabilities produced by social inequalities, fuel the occurrence of major accidents and aggravate their effects, which, by being amplified beyond their spatial and temporal boundaries, especially affect countries in the Global South. We conclude that the recent events represent systemic expressions beyond organizational dysfunctions, revealing deeper layers of organizational and sociotechnical systems such as those forging the global economy and its profound asymmetries.

Oral insulin delivery: utopia, currently possible or a near reality?

Diabetes is still one of the main diseases worldwide due to its high incidence, prevalence and, unfortunately, very high mortality. Type 1 diabetes (and in some other types) is generally controlled by exogenous insulin. Several attempts of oral insulin administration to humans have been done so far. Some of them achieved interesting results, but it seems to exist a barrier to transpose these studies into clinical trials. A broad perspective about the oral insulin and approaches will be addressed. Representative (not all) examples of innovation are herein described, and they should represent a step forward to achieve the main goal: to orally deliver insulin and improve the life quality of millions of patients.

Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P = .015), SAE-free survival (P = .008), and time to recovery (P = .03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS.

A Brief Overview of the Oral Delivery of Insulin as an Alternative to the Parenteral Delivery.

Diabetes mellitus greatly affects the quality of life of patients and has a worldwide prevalence. Insulin is the most commonly used drug to treat diabetic patients and is usually administered through the subcutaneous route. However, this route of administration is ineffective due to the low concentration of insulin at the site of action. This route of administration causes discomfort to the patient and increases the risk of infection due to skin barrier disturbance caused by the needle. The oral administration of insulin has been proposed to surpass the disadvantages of subcutaneous administration. In this review, we give an overview of the strategies to deliver insulin by the oral route, from insulin conjugation to encapsulation into nanoparticles. These strategies are still under development to attain efficacy and effectiveness that are expected to be achieved in the near future.

Novel and revisited approaches in nanoparticle systems for buccal drug delivery.

The buccal route is considered patient friendly due to its non-invasive nature and ease of administration. Such delivery route has been used as an alternative for the delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation, such as occurs in the gastrointestinal tract. However, the drug concentration absorbed in the buccal mucosa is often low to obtain an acceptable therapeutic effect, mainly due to the saliva turnover, tongue and masticatory movements, phonation, enzymatic degradation and lack of epithelium permeation. Therefore, the encapsulation of drugs into nanoparticles is an important strategy to avoid such problems and improve their buccal delivery. Different materials from lipids to natural or synthetic polymers and others have been used to protect and deliver drugs in a sustained, controlled or targeted manner, and enhance their uptake through the buccal mucosa improving their bioavailability and therapeutic outcome. Overall, the main aim of this review is to perform an overview about the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Herein, several types of nanoparticles and delivery strategies are addressed, and a special focus on pipeline products is also given.

Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability.

Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs' passage through biological membranes is very limited. Carriers like phytosomes are promising systems to optimize oral absorption of encapsulated extracts. This work prepared and fully characterized phytosomes containing bioactive phenolic extracts from persimmon in terms of size, surface charge, encapsulation efficiency and stability over six months. These phytosomes were orally dosed to Wistar rats during a 15-day period. Afterwards, haematological and biochemical analyses were performed. Monodisperse phytosomes were successfully prepared, with size less than 300nm (PI < 0.3) and high encapsulation efficiency (97.4%) of PCs. In contrast to free extract, extract-loaded phytosomes had higher antioxidant activity after 6 months storage. Oral administration of extract-loaded phytosomes and free extract did not lead to lipidic profile changes and were within referenced normal ranges, as well as glycaemia levels and urine parameters. The results highlighted the potential of persimmon PCs as food supplements or pharmacological tools, suggesting a promising and safe phytosomal formulation containing bioactive agents of persimmon that could lead to health benefits.

Development of a bioadhesive nanoformulation with Glycyrrhiza glabra L. extract against Candida albicans.

Glycyrrhiza glabra L. is considered an important source of bioactive compounds. This study aimed at the development of an efficient solution for the treatment of oral candidiasis. Several extracts of Glycyrrhiza glabra L. were prepared using different solvents and their potential in vitro antifungal activity was assessed. Ethanolic extracts showed the most promising results against C. albicans. This extract was incorporated into mucoadhesive nanoparticles (PLA, PLGA and alginate), which were further included in an oral gel, an oral film and a toothpaste, respectively. The results showed that nanoparticles were successfully produced, presenting a mean size among 100-900 nm with high encapsulation efficiency. In vitro studies showed that the most bioadhesive formulation was the oral film with extract-loaded PLGA nanoparticles, followed by the toothpaste with extract-loaded alginate nanoparticles and the oral gel with extract-loaded PLA nanoparticles.

Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia.

BACKGROUND/AIMS: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. METHODS: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. RESULTS AND CONCLUSIONS: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.

Past, Recent Progresses and Future Perspectives of Nanotechnology Applied to Antifungal Agents.

Candida species remain a significant cause of nosocomial bloodstream infections, associated with prolonged hospital stay in the ICU and high healthcare cost. The incidence of Candida is very high in certain risk groups of patients (AIDS, diabetes, cancer, etc.). Recent developments of nanotechnology have strongly contributed to the design of new multifunctional drug carriers that improve drug bioavailability through a controlled and prolonged release profile or even through a more specific targeted delivery of the antifungal agent. Those types of systems have strongly increased with a progressive generation of new structures, permitting the conjunction of new materials, biomolecules, physical and chemical techniques, for better outcomes. Nanotechnology shows expanded possibilities within the medical field and in the case of the yeast infections it may overcome several issues related with the fungal proliferation or higher inhibition of the pathogen causing the infection. This review covers a period of the most representative research of Candidiasis since 1993 to the present.

Equipamiento de actividades ancestrales / Equipment for ancestral activities

El proyecto es un equipamiento que tiene por objetivo fortalecer las actividades y conocimientos ancestrales, ofreciendo espacios ceremoniales y de ritualidad, también ofrecerá alternativas a la medicina tradicional. El proyecto tiene 2 diferentes áreas una relaciona a la medicina tradicional y otra que está dedicado a la ritualidad. Uno de los espacios importantes del proyecto es el saumero. El saumero es un espacio de terapia de vapor que con la cual se tratara distintos tipos de enfermedades comunes en nuestra población, como reumatismo, artritis, infecciones, etc. Otro espacio destacado es el vivero, es un espacio que abastecerá lo que es el saumero ya que cada sesión que se realice necesitará distintos tipos de hierbas medicinales según requiera la necesidad del paciente. El relacionamiento social del proyecto se dará con en el tratamiento de actividades ceremoniales y culturales en la ciudad de El Alto, actividades como: carnavales, alasitas, año nuevo aymara, todos los santos, día de los chamakanis, etc. y también con las actividades que realizan diariamente los yatiris como son la lectura de la coca y su diagnóstico. El proyecto se enfocara específicamente a esas actividades que estén relacionados con la medicina alternativa, y la actividad ancestral ya que estos, están ligados de alguna manera, y las dos buscan el bienestar de las personas. (AU)

Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment.

Oral candidiasis is a mycosis on the mucous membranes of the mouth but not limited to the mouth. Nystatin is one of the most frequently employed antifungal agents to treat infections and may be safely given orally as well as applied topically but its absorption through mucocutaneous membranes such as the gut and the skin is minimal. The purpose of this study is to enhance the effectiveness of nystatin using particulate system such as beads, micro- and nanoparticles of alginate incorporated into toothpaste. Those particulate systems of nystatin were prepared by extrusion/external gelation for beads and emulsification/internal gelation for micro- and nanoparticles and characterized. Small, anionic charged and monodispersed particles were successfully produced. The type of particulate system influenced all previous parameters, being microparticles the most suitable particulate system of nystatin showing the slowest release, the highest inhibitory effect of Candida albicans over a period of one year. Those results allowed the conclusion that alginate exhibits properties that enable the in vitro functionality of encapsulated nystatin and thus may provide the basis for new successful approaches for the treatment of oral antifungal infections such as oral candidiasis.

A weighted principal component analysis and its application to gene expression data.

In this work, we introduce in the first part new developments in Principal Component Analysis (PCA) and in the second part a new method to select variables (genes in our application). Our focus is on problems where the values taken by each variable do not all have the same importance and where the data may be contaminated with noise and contain outliers, as is the case with microarray data. The usual PCA is not appropriate to deal with this kind of problems. In this context, we propose the use of a new correlation coefficient as an alternative to Pearson's. This leads to a so-called weighted PCA (WPCA). In order to illustrate the features of our WPCA and compare it with the usual PCA, we consider the problem of analyzing gene expression data sets. In the second part of this work, we propose a new PCA-based algorithm to iteratively select the most important genes in a microarray data set. We show that this algorithm produces better results when our WPCA is used instead of the usual PCA. Furthermore, by using Support Vector Machines, we show that it can compete with the Significance Analysis of Microarrays algorithm.