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Viruses are important agents of emerging zoonoses and are a substantial public health issue. Among emerging viruses, an important group are arboviruses, which are characterized by being maintained in nature in cycles involving hematophagous arthropod vectors and a wide range of vertebrate hosts. Recently, bats have received increasing attention as an important source for the emergence of zoonoses and as possible viral reservoirs. Among the arboviruses, there are many representatives of the genera Flavivirus and Alphavirus, which are responsible for important epidemics such as Dengue virus, Zika virus and Chikungunya virus. Due to the importance of analyzing potential viral reservoirs for zoonosis control and expanding our knowledge of bat viruses, this study aimed to investigate the presence of viruses of the Alphavirus and Flavivirus genera in bats. We analyzed serum, liver, lungs and intestine from 103 bats sampled in northeast and southern Brazil via Nested-PCR and the hemagglutination inhibition test. All samples tested in this study were negative for arboviruses, suggesting that no active or past infection was present in the captured bats. These data indicate that the bats examined herein probably do not constitute a reservoir for these viruses in the studied areas. Further studies are needed to clarify the role of bats as reservoirs and sources of infection of these viral zoonoses.

Introduction  Opioids are the mainstay of pain management in critically ill patients. However, recent attention to their adverse effects in the intensive care unit (ICU) has led to the use of strategies that aim to reduce these side effects. Among these strategies, there are multimodal analgesia protocols, which prioritize pain management and employ a combination of different analgesics to spare excessive doses of opioids and sedatives in continuous infusion. Objective The objective of this study is to evaluate the impact of a multimodal analgesia protocol on clinical outcomes and consumption of sedatives and analgesics in two intensive care units. Methods  We conducted a single-center, quasi-experimental, retrospective, and prospective cohort study comparing clinical outcomes and consumption of sedatives and analgesics before and after the implementation of a multimodal pain management protocol in critically ill adult patients. We included 465 patients in 2017 (pre-intervention group) and 1508 between 2018 and 2020 (post-intervention group). Results In the analysis of the primary outcome, there was a significant reduction in mortality between 2017 and 2020 (27.7% - 21.7%, p=0.0134). There was no statistical difference in mechanical ventilation time or concerning the infection rate. Patients who received the multimodal analgesia protocol had a decrease of 24% regarding mean fentanyl intake and a progressive reduction in morphine milligram equivalents (MME) (8.4% - 19%). There was an increasing trend in the use of adjuvant analgesics and morphine in preemptive and therapeutic analgesia. Conclusion The implementation of a multimodal pain control protocol significantly reduced morbidity and mortality and the use of opioids in the ICU.

São Paulo (SP), a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in SP, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in SP, we generated and analysed virus genomic data and epizootic case data from NHP in SP. We report the occurrence of three spatiotemporally distinct phases of the outbreak in SP prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in SP, mostly sampled from non-human primates between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in SP state at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern SP subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of SP state. Our results shed light on the sylvatic transmission of yellow fever in highly fragmented forested regions in SP state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species. Competing Interest Statement The authors have declared no competing interest.

Background In many regions of the world, K is being depleted from soils due to agricultural intensification a lack of accessibility, and the high cost of K. Thus, there is an urgent need for a sustainable strategy for crops in this environment. Si is an option for mitigating stress due to nutritional deficiency. However, the underlying effects of Si in mitigating K deficiency C:N:P homeostasis still remains unknown for bean plants. This is a species of great worldwide importance. Thus, this study aims to evaluate whether i) K deficiency modifies the homeostatic balance of C, N and P, and, if so, ii) Si supply can reduce damage caused to nutritional stoichiometry, nutrient use efficiency, and production of dry mass in bean plants. Results K deficiency caused a reduction in the stoichiometric ratios C:N, C:P, and P:Si in shoots and C:N, C:P, C:Si, N:Si, and P:Si in roots, resulting in a decrease in K content and use efficiency and reducing biomass production. The application of Si in K-deficient plants modified the ratios C:N, C:Si, N:P, N:Si, and P:Si in shoots and C:N, C:P, C:Si, N:Si, N:P, and P:Si in roots, increasing the K content and efficiency, reducing the loss of biomass. In bean plants with K sufficiency, Si also changed the stoichiometric ratios C:N, C:P, C:Si, N:P, N:Si, and P:Si in shoots and C:N, C:Si, N:Si, and P:Si in roots, increasing K content only in roots and the use efficiency of C and P in shoots and C, N, and P in roots, increasing the biomass production only in roots. Conclusion K deficiency causes damage to the C:N:P homeostatic balance, reducing the efficiency of nutrient use and biomass production. However, Si is a viable alternative to attenuate these nutritional damages, favoring bean growth. The future perspective is that the use of Si in agriculture in underdeveloped economies with restrictions on the use of K will constitute a sustainable strategy to increase food security.

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.

In this randomized trial comparing rivaroxaban with dose-adjusted warfarin in patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months.

Background C:N:P homeostasis in plants guarantees optimal levels of these nutrients in plant metabolism. H However, one of the causes to the effects of deficit irrigation is the loss of C:N:P homeostasis in leaves and stems that causes reduction in the growth of sugarcane. Being able to measure the impact of water deficit on C:N:P homeostasis in plants from the stoichiometric ratios of the concentrations of these nutrients in leaves and stems. This loss causes a decrease in nutritional efficiency, but can be mitigated with the use of silicon. Silicon favors the homeostasis of these nutrients and crop productivity. The magnitude of this benefit depends on the absorption of Si by the plant and Si availability in the soil, which varies with the type of soil used. Thus, this study aims to evaluate whether the application of Si via fertigation is efficient in increasing the absorption of Si and whether it is capable of modifying the homeostatic balance of C:N:P of the plant, causing an increase in nutritional efficiency and consequently in the production of biomass in leaves and stems of sugarcane ratoon cultivated with deficient and adequate irrigations in different tropical soils. Results Water deficit caused biological losses in concentrations and accumulation of C, N, and P, and reduced the nutrient use efficiency and biomass production of sugarcane plants cultivated in three tropical soils due to disturbances in the stoichiometric homeostasis of C:N:P. The application of Si increased the concentration and accumulation of Si, C, N, and P and their use efficiency and reduced the biological damage caused by water deficit due to the modification of homeostatic balance of C:N:P by ensuring sustainability of the production of sugarcane biomass in tropical soils. However, the intensity of attenuation of such deleterious effects stood out in plants cultivated in Eutrophic Red Oxisols. Si contributed biologically by improving the performance of sugarcane ratoon with an adequate irrigation due to the optimization of stoichiometric ratios of C:N:P; increased the accumulation and the use efficiency of C, N, and P, and promoted production gains in biomass of sugarcane in three tropical soils. Conclusion Our study shows that fertigation with Si can mitigate the deleterious effects of deficient irrigation or potentiate the beneficial effects using an adequate irrigation system due to the induction of a new stoichiometric homeostasis of C:N:P, which in turn improves the nutritional efficiency of sugarcane cultivated in tropical soils.

Silicon (Si) may be involved in the modification of C:N:P stoichiometry and in physiological processes, increasing sorghum growth and grain production. The objective was to evaluate the effect of Si supply on C:N:P:Si stoichiometry, physiological response, growth, and grain production of sorghum. The experiment was carried out in pots with four concentrations of Si: 0; 1.2; 2.4; and 3.6 mmol L −1 in a completely randomized design, with six replicates. Physiological attributes and dark green color index were measured and grain and biomass production were determined. Posteriorly, the plant material was ground to determine silicon (Si), carbon (C), nitrogen (N), and phosphorus (P) contents in order to analyze C:N:P:Si stoichiometry. C:Si and C:N ratios decreased at all Si concentrations applied (1.2, 2.4, and 3.6 mmol L −1 ) and in all plant parts studied, being lower at 3.6 mmol L −1 . The lowest C:P ratios of leaves and roots were observed at 3.6 mmol L −1 Si and the lowest C:P ratio of stems was observed at 1.2 mmol L −1 Si. Si concentrations were not significant for the N:P ratio of leaves. The highest N:P ratio of stems was observed at 3.6 mmol L −1 , while the lowest N:P ratio of roots was observed at 2.4 and 3.6 mmol L −1 . Regardless of photosynthetic parameters, the application of 1.2 mmol L −1 Si enhanced photosynthetic rate. The application of 2.4 and 3.6 mmol L −1 enhanced stomatal conductance and dark green color index. The mass of 1000 grains was not influenced by Si applications, while Si applications at all concentrations studied (1.2, 2.4, and 3.6 mmol L −1 ) enhanced shoot and total dry matter, not affecting root dry matter and grain production. In conclusion, Si supply modifies C:N:P:Si stoichiometry and increases physiologic parameters, growth, development, and grain production in sorghum.

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.