Pontifícia Universidade Católica de Campinas

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).

In relation to the first edition of the bookpublished in 2009, this second edition, brings significantadvances, specifically regarding new terminology andin the classification of disorders, today’s terms replaceolder ones or are included side by side, and new materialpublished since then is coved.The book is organized into four parts: clinicalaspects, experimental aspects, theoretical aspects, andtreatment of depression. Part I describes the definition,symptoms, course and prognosis of depression, as wellas ratings of mood disorders, depression, psychoticversus nonpsychotic depression, bipolar disorders,involutional depression and schizoaffective disorder.Part II reports biological and psychological studies ofdepression, including psychoanalytic theory tests. PartIII investigates theories of depression, cognition andpsychopathology and the development of depression.Part IV describes the main treatments for depression,including the somatic therapies, psychotherapy and theassessment of treatments for depression: randomcontrolled trials.Part I presents the questions about depressionthat are present throughout human history. Even thoughit has been recognized as a clinical syndrome for overtwo thousand years, an entirely satisfactory explanationof its intriguing and paradoxical features has not beenfound. There are few psychiatric syndromes in whichthe clinical definitions are so constant throughoutconsecutive periods of history. The nature and etiologyof depression are subject to different concepts. Somescholars ensure that depression is a psychogenicdisorder, while others claim that it is caused by organicfactors. A third group believes in two different types ofdepression: one psychogenic and the other organic.Schizophrenia and depression constitute the firstand second most common diagnoses, respectively, foradmissions to psychiatric hospitals in the United States,and the prevalence of depression outside psychiatrichospitals is evaluated as being five times that ofschizophrenia. According to the fourth edition of theDiagnostic and Statistical Manual of Mental Disorders(DSM-IV) of the American Psychiatric Association (APA),the likelihood of developing major depressive disorderduring life is from 12% to 15% for men and from 10% to25% for women. Major depressive disorder is the mainreason for disability in strengthened market economiesaround the world.In

Experience economy is the last segment in the evolution of the market, and it is characterized by the fact that consumers do not acquire goods, products or services, but experiences that they integrate in their biography, and consequently in their identity. Customer Experience, possibly the latest revolution in business thinking along with the digital transformation, seeks the design and management of truly customer-centric experiences. This revolution is spreading across different sectors, among which the health sector should necessarily be considered. This talk covers the fundamental ideas within the concept of customer experience, as well as it provides information and suggestions about how to design and deliver an optimal patient experience.

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

Carbenes are important intermediates in organic chemistry and have been widely applied in various types of organic reactions, ranging from cycloaddition reactions and sigmatropic rearrangements to C-H functionalizations, thus allowing the rapid construction of densely functionalized molecules. Over the past decades, remarkable progress has been achieved in metal-catalyzed carbene transfer reactions. Nevertheless, realizing these transformations under milder and/or greener conditions is still highly desirable. Only recently, visible light-promoted carbene transfer reactions of diazo compounds via free carbene intermediates have emerged as a practical, mild and powerful tool. In this tutorial review, we summarize the latest advances in the area, aiming at providing a clear overview on reaction design, mechanistic scenarios and potential future developments.

Resumo Considerando-se a situação atual mundial, marcada por importantes crises na saúde pública e, mais recentemente, a pandemia causada pela COVID-19, o presente artigo buscou reunir informações e achados de pesquisa a respeito do impacto de tais crises na saúde mental. O texto traz conceitos relacionados à problemática do novo coronavírus e analisa consequências de medidas adotadas para lidar com situações desse tipo, tais como distanciamento social, quarentena e isolamento, ao longo de três períodos distintos: pré-crise, intracrise e pós-crise. O artigo enfoca as repercussões observadas na saúde mental da população, refletindo acerca dos desfechos favoráveis e desfavoráveis dentro do processo de crise. Por fim, são apresentadas questões relacionadas à emergência do cuidado em saúde mental, tanto aquele prestado pela Psicologia, como aquele que pode ser desenvolvido pelos demais profissionais de saúde, de modo a minimizar os impactos negativos da crise e atuar de modo preventivo.

BACKGROUND: Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. METHODS: In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. RESULTS: As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. CONCLUSIONS: Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).

ᅟ: Obstruction and perforation due to colorectal cancer represent challenging matters in terms of diagnosis, life-saving strategies, obstruction resolution and oncologic challenge. The aims of the current paper are to update the previous WSES guidelines for the management of large bowel perforation and obstructive left colon carcinoma (OLCC) and to develop new guidelines on obstructive right colon carcinoma (ORCC). Methods: The literature was extensively queried for focused publication until December 2017. Precise analysis and grading of the literature has been performed by a working group formed by a pool of experts: the statements and literature review were presented, discussed and voted at the Consensus Conference of the 4th Congress of the World Society of Emergency Surgery (WSES) held in Campinas in May 2017. Results: CT scan is the best imaging technique to evaluate large bowel obstruction and perforation. For OLCC, self-expandable metallic stent (SEMS), when available, offers interesting advantages as compared to emergency surgery; however, the positioning of SEMS for surgically treatable causes carries some long-term oncologic disadvantages, which are still under analysis. In the context of emergency surgery, resection and primary anastomosis (RPA) is preferable to Hartmann's procedure, whenever the characteristics of the patient and the surgeon are permissive. Right-sided loop colostomy is preferable in rectal cancer, when preoperative therapies are predicted.With regards to the treatment of ORCC, right colectomy represents the procedure of choice; alternatives, such as internal bypass and loop ileostomy, are of limited value.Clinical scenarios in the case of perforation might be dramatic, especially in case of free faecal peritonitis. The importance of an appropriate balance between life-saving surgical procedures and respect of oncologic caveats must be stressed. In selected cases, a damage control approach may be required.Medical treatments including appropriate fluid resuscitation, early antibiotic treatment and management of co-existing medical conditions according to international guidelines must be delivered to all patients at presentation. Conclusions: The current guidelines offer an extensive overview of available evidence and a qualitative consensus regarding management of large bowel obstruction and perforation due to colorectal cancer.

The scientific and industrial communities have been giving great attention to the development of new bio-based materials with potential use in innovative technological applications. Among these materials are the structures with gel-like behavior that can be used in the cosmetic, pharmaceutical and food industries, aiming at controlling the physical properties of the final products. In the past ten years, words like oleogels and organogels have been increasingly used, the existing number of manuscripts and patents being proof of this tendency. In the food industry, oleogels can be used to control phase separation, and decrease the mobility and migration of the oil phase, providing solid-like properties without using high levels of saturated fatty acids as well as to be a carrier of bioactive compounds. In most cases, their main features are related to the reorganization process of gelators after an increase of the temperature, above the melting or glass transition temperature of the materials, known as the direct method, but it is also possible to develop oleogels by indirect methods, such as emulsification and the solvent exchange technique. In the direct methods, the reorganization is able to physically entrap oil leading to different physicochemical properties, the rheological behavior and texture properties being the frequently most studied ones. This review overviews the use of food grade and bio-based structurants to produce edible oleogels, aiming at fat replacement and structure-tailoring. Gelation mechanisms and oil phases used during oleogel production are discussed, as well as the current food applications and future trends for this kind of structure.

As avaliações de dietas e o planejamento de consumo são atividades tradicionalmente realizadas por meio da comparação de médias de ingestão contra valores de referência de energia e nutrientes, seja para indivíduos ou grupos. Limitações de ordem técnica devem ser levadas em conta, sem as quais se pode chegar a conclusões equivocadas quanto ao atendimento das necessidades nutricionais. As Recomendações Nutricionais propostas pelo Institute of Medicine dos Estados Unidos, em conjunto com a agência Health Canada, a partir de 1997, conhecidas como Dietary Reference Intakes, representam um novo paradigma para o estabelecimento de indicadores nutricionais de consumo, ao aperfeiçoarem o uso do conceito de risco na avaliação de dietas. Fontes de erro intra ou interindividuais, devidas à variabilidade de padrão de consumo e decorrentes da distribuição das necessidades na população, aliadas a um pequeno número de dias de observação, têm grande impacto sobre a confiabilidade da análise. Por esta razão devem orientar a utilização dos valores, que foram organizados em tabelas com as quatro categorias de nutrientes, publicadas entre 1997 e 2005. O presente trabalho teve por objetivo destacar algumas características de aplicação e consolidar os valores diários de Tolerable Upper Intake Level, Adequate Intake e Recommended Dietary Allowance, facilitando a consulta por parte de profissionais e estudantes da área de nutrição.

Essa obra configura um momento em um processo de pesquisas sobre "as relações com o saber" e com a escola de jovens que estudam na periferia, na França. Tais pesquisas são desenvolvidas na Universidade de Paris VIII pela equipe da Educação, Socialização e Coletividades Locais -ESCOL. É o resultado de um aprofundamento realizado pelo autor, que visa explicar os motivos que o levam a tratar questões usualmente consideradas como "fracasso escolar", origem social e deficiências socioculturais como "relação com o saber". Portanto, o livro é um momento centrado especificamente na elaboração de uma teoria da "relação com o saber" que, a princfpio, visava ser suporte para a interpretação dos dados coletados pelos pesquisadores da ESCOL e, felizmente, veio a se tornar um apoio para nossas pesquisas e mesmo nossas inquietações pessoais.

The widespread use of pesticides in agriculture can lead to water contamination and cause adverse effects on non-target organisms. Brazil has been the world's top pesticide market consumer since 2008, with 381 approved pesticides for crop use. This study provides a comprehensive literature review on the occurrence of pesticide residues in Brazilian freshwaters. We searched for information in official agency records and peer-reviewed scientific literature. Risk quotients were calculated to assess the potential risk posed to aquatic life by the individual pesticides based on their levels of water contamination. Studies about the occurrence of pesticides in freshwaters in Brazil are scarce and concentrated in few sampling sites in 5 of the 27 states. Herbicides (21) accounted for the majority of the substances investigated, followed by fungicides (11), insecticides (10) and plant growth regulators (1). Insecticides are the class of major concern. Brazil would benefit from the implementation of a nationwide pesticide freshwater monitoring program to support preventive, remediation and enforcement actions.

A comensalidade contemporânea é aqui discutida, focalizando particularmente o impacto nas mudanças alimentares urbanas, fundamentando-se em autores das ciências sociais que discutem a globalização. Abordou-se o processo pelo qual alimentos e serviços são desterritorializados e alcançam um caráter global, visando contribuir para estudos sobre as mudanças alimentares e analisar outras dimensões, além das nutricionais, do que se denomina dieta afluente.

This paper reports the comparison of the electrochemical properties of 3D PLA-graphene electrodes (PLA-G) under different activation conditions and through different processes. In this work, the performance of the electrodes was evaluated after polishing, electrochemical and chemical treatments and a combination of them. The best results were obtained with hydroxide activation using 1.0 mol L-1 NaOH for 30 min of immersion, which promoted the saponification of PLA exposing the graphene nanoribbon structures. The improvement was more evident also after electrochemical activation, which led to a great increase in surface area, defects, electron transfer rate and amount of edge sites. The analytical performance of the proposed PLA-GNaOH-30-EC electrode was evaluated in the presence of dopamine (DA) by three electrochemical techniques, presenting a broad linear range, and limits of detection of 3.49, 2.17 and 1.67 μmol L-1 were obtained by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV), respectively. The separation and quantification of DA in the presence of AA and UA was also reported. The sensor showed good repeatability and reproducibility and was successfully applied to DA determination in synthetic urine and human serum, showing good recovery, from 88.8 to 98.4%. Therefore, the activation methods were essential for the improvement in the 3D PLA-G electrode properties, allowing graphene surface alteration and electrochemical enhancement in the sensing of molecular targets.

The arrangement of water molecules at charged aqueous interfaces is an important question in biology, electrochemistry, and geochemistry. Theoretical studies suggest that the molecules become arranged in several layers adjacent to a solid interface. Using atomic force microscopy we have measured the water dielectric-permittivity profile perpendicular to mica surfaces. The measured variable permittivity profile starting at epsilon approximately 4 at the interface and increasing to epsilon=80 about 10 nm from the surface suggests a reorientation of water molecule dipoles in the presence of the mica interfacial charge.

Hitherto implemented economic mechanisms and development processes have led the planet to face numerous environmental and ecological depletion challenges. In light of this, Circular Economy emerges as an effective tool for triggering a sustainable development process. This article aims to present different perspectives and concepts of circular economy. To that end, a qualitative study was conducted and the methodology of systematic literature review was applied, so as to obtain solid knowledge about the theme, using the most recent and relevant articles. Scielo, Science Direct and Google Scholar database were the source of the articles that met the defined criteria, described in six steps: search key words; only scientific articles considered; publication between 2015 and 2020; in English; with 100 or more citations; relevant content to the theme. As a result, an extract of the researched articles and a comparison between the scientific literature on this subject is presented, showing some evolution of the aspects of the Circular Economy, such as designing of new products, emerging of new legislation and adoption by industry. Although the study was not conclusive on how the evolution of Circular Economy will take place, authors suggest future studies to assess the transition towards an economic circularity. Also, it is recommended that future studies consider case studies as a model for assessing Ciruclar Economy progress in the light of legislation and economic interests.

The boom in visible light photoredox catalysis (VLPC) research has demonstrated that this novel synthetic approach is here to stay. VLPC enables reactive radical intermediates to be catalytically generated at ambient temperature, a feat not generally allowed through traditional pyrolysis- or radical initiator-based methodologies. VLPC has vastly extended the range of substrates and reaction schemes that have been traditionally the domain of radical reactions. In this review the photophysics background of VLPC will be briefly discussed, followed by a report on recent inroads of VLPC into decarboxylative couplings and radical C-H functionalization of aromatic compounds. The bulk of the review will be dedicated to advances in synergistic catalysis involving VLPC, namely the combination of photoredox catalysis with organocatalysis, including β-functionalization of carbonyl groups, functionalization of weak aliphatic C-H bonds, and anti-Markovnikov hydrofunctionalization of alkenes; dual catalysis with gold or with nickel, photoredox catalysis as an oxidation promoter in transition metal catalysis, and acid-catalyzed enantioselective radical addition to π systems.

AIM: The aim of the study is to compare the prevalence of depression in women surgically diagnosed with endometriosis according to the presence or absence of pelvic pain. METHODS: This cross-sectional prospective study evaluated 100 women receiving care at the Outpatients' Clinic for Endometriosis, Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil, equally divided into two groups: one suffering from chronic pelvic pain and the other pain-free. The Beck Depression Inventory was used in order to measure depression. RESULTS: Depression was detected in 86 and 38% of the women with and without chronic pelvic pain, respectively. Complaints of depression, such as somatic concerns, work inhibition, dissatisfaction, and sadness, were observed at a significantly higher rate in the group with pain. A sensation of failure was the only variable observed more frequently in the pain-free group. CONCLUSIONS: Depression is highly prevalent in women with endometriosis, especially those with pelvic pain. Careful evaluation can identify women with depression who may benefit from 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.

The last decade saw the development of electrochemical paper-based analytical devices (ePADs).