On some adventures in dynamic combinatorial chemistry

La chimica dinamica combinatoria è una disciplina della chimica moderna che ha per oggetti del suo studio i sistemi complessi costituiti da miscele di composti che sono in grado di scambiare componenti l’uno con l’altro mediante reazioni reversibili. I principi della chimica dinamica combinatoria sono stati applicati efficacemente in numerosi campi, quali ad esempio la ricerca di recettori o di sostanze bioattive, la preparazione di polimeri dinamici, lo studio di molecole topologicamente non banali, lo sviluppo di sensori e l'investigazione di sistemi auto-replicanti. Questa tesi di dottorato presenta una serie di lavori condotti nella cornice di questa interessante disciplina.Dynamic combinatorial chemistry is a discipline of modern chemistry whose objects of the study are the complex systems constituted by mixtures of compounds that are able to exchange subcomponents through reversible reactions. The principles of dynamic combinatorial chemistry have been effectively applied in many fields of research, such as the search for receptors or bioactive compounds, the preparation of dynamic polymers, the study of topologically nontrivial molecules, the development of sensors and the investigation of self-replicating systems. This doctoral thesis presents a number of works carried out within the frame of this interesting discipline

Memory and (re)creation in teacher education: treading paths

This work presents partial results of a research on the training possibilities established by the relations among memory, creation and teacher education. It brings reflections about the training practice developed with students of the Graduation in Pedagogy of the State University of Campinas. Those reflections intend to establish relations between the processes of remembering and of creating theatrical narratives experienced by the students, expecting that those relations can contribute to the research and practices of teacher education. The theoretical framework is basically constituted by the studies of self-biographic approach and concepts of the Analytical Psychology of Carl Gustav Jung. This analysis results in the identification of creation processes as a privileged space to produce and draw up symbols allowing to ordinate has been experienced through the acts of remembering, staging life stories, writing and drawing from the experiences lived.Este trabalho apresenta resultados parciais de uma pesquisa sobre as possibilidades formativas estabelecidas na relação entre memória, criação e formação docente. O texto traz reflexões sobre aspectos de uma prática de formação realizada com alunas do curso de Pedagogia da Universidade Estadual de Campinas. Objetivamos, com esta reflexão, estabelecer relações entre os processos de rememoração e de criação de narrativas cênicas vivenciados pelas alunas, na perspectiva de que essas relações venham a contribuir para a pesquisa e as práticas de formação docente. Constituem os referenciais teóricos deste trabalho estudos sobre a pesquisa (auto)biográfica e aportes da Psicologia Analítica de Carl Gustav Jung. Resulta dessa análise a identificação dos processos de criação como espaços privilegiados para a produção e elaboração de símbolos, potencializando a ordenação do vivido por meio do rememorar, do encenar histórias de vida e do registro das experiências de formação com palavras e imagens.10511

Lower lip squamous cell carcinoma in patients with photosensitive disorders : analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012

Lower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC. Data from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients? medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher?s exact test. Survival curves were constructed using the Kaplan?Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package. The mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients. Photosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected

Avaliação de um programa de benefícios de medicamentos em farmácias / Evaluation of a program of benefits of pharmacy medicines

O objetivo deste trabalho foi realizar o levantamento sobre medicamentos integrantes de um Programa de Beneficiamento de Medicamentos implementado por uma rede de farmácias no interior do Rio Grande do Sul. Trata-se de uma pesquisa observacional de caráter  documental. O estudo foi realizado entre meses de julho e agosto do ano de 2018 em uma filial de uma rede de farmácias comunitária do Estado do Rio Grade do Sul. Verificou-se as variáveis relacionada aos medicamentos como nome dos laboratórios, nome da medicação referência, finalidade terapêutica, especialidade médica do prescritor, apresentação farmacêutica, preço da medicação, percentual de desconto e valor com desconto no ato da compra.  Os dados foram cedidos  pelo estabelecimento farmacêutico mediante convênio firmado com o Curso de Farmácia do Centro de Ciências da Saúde- URCAMP (RS). Foi possível observar a participação de 11 laboratórios no PBM, sendo medicamentos mais vendido os bloqueadores da angiotensina II (25%), indicados para hipertensão arterial. As especialidades médicas mais beneficiadas com o PBM são a cardiologia seguida da endocrinologia. Verificou-se que no período do estudo  os medicamentos elencados na PBM obtiveram  descontos que variaram entre 20 à 59%. Em relação aos medicamentos mais vendidos o Alenia® (Biosintético) representou um total de 60 unidades, seguido de Yaz®  (42) (Bayer) e do Nexiun® (40) (Astra Zeneca). Em relação ao percentual de descontos Lípitor® (Pfazier) é o medicamento que obteve até 59% de descontos dado pelo laboratório, seguido do Diovan® (Novartis) com 52%. O PBM está permitindo a acessibilidade de alguns medicamentos onerosos assim como a possibilidade de manter o tratamento de doenças cardiovasculares, respiratórias e metabólicas. 

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Simple SummaryEmerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process.Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-beta 1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Teatro na formação do educador da infância: experiências e possibilidades

We present, in this article, aspects of a teacher training practice at the Faculty of Education at the University of Campinas (Unicamp), which was part of a doctoral research. This research is configured as a research-training to encompass the concomitant use of teacher training activities and research activities. The aspects discussed here refer to the experiences of the students, future teachers, with elements of drama. The dramatic games allowed the future teachers to experience daydream and the creative thinking charactistic of poetry. The whole process was recorded on audio and video. From the observation and analysis of the activities performed during the training process, we discussed the importance of creative experience as constitutive of the constant process of becoming an educator. Studies on drama and on education through the arts directed these reflections