Carboplatin is a derivative of cisplatin; it has a similar mechanism of action, but differs in terms of structure and toxicity. It was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several tumor types. This agent is characterized by its ability to generate lesions in DNA through the formation of adducts with platinum, thereby inhibiting replication and transcription and leading to cell death. However, its use can lead to serious inconvenience arising from the development of resistance that some patients acquire during treatment, limiting the scope of its full potential. Currently, the biochemical mechanisms related to resistance are not precisely known. Therefore, knowledge of pathways associated with resistance caused by carboplatin exposure may provide valuable clues for more efficient rational drug design in platinum-based therapy and the development of new therapeutic strategies. In this narrative review, we discuss some of the known mechanisms of resistance to platinum-based drugs, especially carboplatin.

The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NEDDylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance.

The Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. In 2020 between the 17th and 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 h after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatalities associated with COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.6%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy countrywise could have contributed to a better control of the COVID-19 spread in Brazil. Quarantine decree by the local administration, comprehensive molecular testing coupled to scientific analysis of COVID-19 spreading, prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

Objective To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients’ immunological response. Methods Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17–39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.

Since the first reported case of COVID-19 in Brazil, the public and private educational system started to close. Up to November 2020, scientific discussions about the return of schooling activities have been rarely performed by the national scientific community and police-makers. The great delay of school returning in Brazil contrasts with successful international strategies of school reopening worldwide and seems counterintuitive with the reopening of non-essential activities. Here, important issues to be considered before and during school reopening are reviewed and discussed. COVID-19 testing is essential to avoid disease spreading, but high cost of individual RT-qPCRs impairs an extensive testing strategy for school returning. To reduce costs and increase the speed of diagnosis, we tested the efficiency of a pooled-sample PCR strategy in a cohort of the educational staff in the city of Macaé/RJ, finding five asymptomatic individuals (0,66%) among the 754 people tested. Thus, a polled-sample PCR testing strategy of the educational staff might prevent infection spreading in schools at a reasonable cost. We discuss how our test strategy could be coupled with internationally recognized safety rules to allow for a safe school return and how countries from different world regions are dealing with educational activities during COVID-19 pandemic.

No abstract

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.92%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy country wise would have saved over 50,000 lives. Interpretation: Quarantine decree by the local government, molecular massive testing coupled to scientific analysis of COVID-19 spreading prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account gender, vaccination, hospitalization and age. Fatigue and myalgia were the most common symptoms and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant for the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.