Involvement of political and socio-economic factors in the spatial and temporal dynamics of COVID-19 outcomes in Brazil: A population-based study.

Background: Brazil has been severely impacted by COVID-19 pandemics that is aggravated by the absence of a scientifically-driven coordinated informative campaign and the interference in public health management, which ultimately affected health measures to avoid SARS-CoV2 spread. The decentralization and resultant conflicts in disease control activities produced different protection behaviours and local government measures. In the present study, we investigated how political partisanship and socio-economic factors determined the outcome of COVID-19 at the local level in Brazil. Methods: A retrospective study of COVID-19 deaths was carried out using mortality databases between Feb 2020, and Jun 2021 for the 5570 Brazilian municipalities. Socio-economic parameters including city categories, income and inequality indexes, health service quality and partisanship, assessed by the result of the second round of the 2018 Brazilian presidential elections, were included. Regression tree analysis was carried out to identify the statistical significance and conditioning relationships of variables. Findings: Municipalities that supported then-candidate Jair Bolsonaro in the 2018 elections were those that had the worst COVID-19 mortality rates, mainly during the second epidemic wave of 2021. This pattern was observed even considering structural inequalities among cities. Interpretation: In general, the first phase of the pandemic hit large and central cities hardest, while the second wave mostly impacted Bolsonarian municipalities, where scientific denialism among the population was stronger. Negative effects of partisanship towards the right-wing on COVID-19 outcomes counterbalances favourable socioeconomic indexes in affluent Brazilian cities. Our results underscore the fragility of public health policies which were undermined by the scientific denialism of right-wing supporters in Brazil. Funding: International joint laboratories of Institute de Recherche pour le Développement, a partnership between the University of Brasília and the Oswaldo Cruz Foundation (LMI-Sentinela - UnB - Fiocruz - IRD), Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq).

Mechanical Permeabilization as a New Method for Assessment of Mitochondrial Function in Insect Tissues.

Respirometry analysis is an effective technique to assess mitochondrial physiology. Insects are valuable biochemical models to understand metabolism and human diseases. Insect flight muscle and brain have been extensively used to explore mitochondrial function due to dissection feasibility and the low sample effort to allow oxygen consumption measurements. However, adequate plasma membrane permeabilization is required for substrates/modulators to reach mitochondria. Here, we describe a new method for study of mitochondrial physiology in insect tissues based on mechanical permeabilization as a fast and reliable method that do not require the use of detergents for chemical permeabilization of plasma membrane, while preserves mitochondrial integrity.

Responsible Science Assessment: downplaying indexes, boosting quality.

Scientists are facing enormous pressures posed by growing scientific communities and stagnant/reduced funding. In this scenario, mechanisms of knowledge achievement and management, as well as how recruitment, progression and evaluation are carried out should be reevaluated. We argue here that knowledge has become a profitable commodity and, as a consequence, excessive academic quantification, individual output assessment problems and abusive editorial market strategies have reached unsustainable levels. We propose to reinforce existing guidelines and to establish new ones to overcome these issues. Our proposal, the Initiative for Responsible Scientific Assessment (IRSA), has the main goal to strengthen and expand previous movements in the scientific community to promote higher quality research assessment, focused on better Science.

Assessment of mitochondrial physiology of murine white adipose tissue by mechanical permeabilization and lipid depletion.

White adipose tissue (WAT) represents a major site of triacylglycerol energy storage and is directly associated with metabolic disorders. Mitochondria regulate cellular energy expenditure and are active in WAT. Although isolated mitochondria have been classically used to assess their functions, several artifacts can be introduced by this approach. Furthermore, important limitations exist in the available methods to determine mitochondrial physiology in permeabilized WAT. Here, we established and validated a method for functional evaluation of mice mesenteric WAT (mWAT) mitochondria by using MEchanical Permeabilization and LIpid DEpletion (MEPLIDE) coupled to high-resolution respirometry. We observed that mild stirring of mWAT for 20 min at room temperature with 4% fatty acid-free albumin (FAF-BSA) followed by 50 min without FAF-BSA selectively permeabilized white adipocytes plasma membrane. In these conditions, mWAT mitochondria were intact, exhibiting succinate-induced respiratory rates that were sensitive to classical oxidative phosphorylation modulators. Finally, the respiratory capacity of mWAT in female mice was significantly higher than in males, an observation that agrees with reported data. Therefore, the functional assessment of mWAT mitochondria through MEPLIDE coupled to high resolution respirometry proposed here will contribute to a better understanding of WAT biology in several pathophysiological contexts.

A simple and reliable method for longitudinal assessment of untethered mosquito induced flight activity.

Aedes aegypti adult females are key vectors of several arboviruses and flight activity plays a central role in mosquito biology and disease transmission. Available methods to quantify mosquito flight usually require special devices and mostly assess spontaneous locomotor activity at individual level. Here, we developed a new method to determine longitudinal untethered adult A. aegypti induced flight activity: the INduced FLight Activity TEst (INFLATE). This method was an adaptation of the "rapid iterative negative geotaxis" assay to assess locomotor activity in Drosophila and explore the spontaneous behavior of mosquitoes to fly following a physical stimulus. Insects were placed on a plastic cage previously divided in four vertical quadrants and flight performance was carried out by tapping cages towards the laboratory bench. After one minute, the number of insects per quadrant was registered by visual inspection and categorized in five different scores. By using INFLATE, we observed that flight performance was not influenced by repeated testing, sex or 5% ethanol intake. However, induced flight activity was strongly affected by aging, blood meal and inhibition of mitochondrial complex I. This simple and rapid method allows the longitudinal assessment of induced flight activity of multiple untethered mosquitoes and may contribute to a better understanding of A. aegypti dispersal biology.

A comparative assessment of mitochondrial function in epimastigotes and bloodstream trypomastigotes of Trypanosoma cruzi.

Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas' disease. The life cycle of T. cruzi is complex and involves different evolutive forms that have to encounter different environmental conditions provided by the host. Herein, we performed a functional assessment of mitochondrial metabolism in the following two distinct evolutive forms of T. cruzi: the insect stage epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate the entry of electrons into the electron transport chain by increasing complex II-III activity. Interestingly, cytochrome c oxidase (CCO) activity and the expression of CCO subunit IV were reduced in bloodstream forms, creating an "electron bottleneck" that favored an increase in electron leakage and H(2)O(2) formation. We propose that the oxidative preconditioning provided by this mechanism confers protection to bloodstream trypomastigotes against the host immune system. In this scenario, mitochondrial remodeling during the T. cruzi life cycle may represent a key metabolic adaptation for parasite survival in different hosts.