Rocio virus (ROCV) was the causative agent of an unprecedented outbreak of encephalitis during the 1970s in the Vale do Ribeira, Sao Paulo State, in the Southeast region of Brazil. Surprisingly, no ...further cases of ROCV infection were identified after this outbreak; however, serological surveys have suggested the circulation of ROCV among humans and animals in different regions of Brazil. Cross-protective immunity among flaviviruses is well documented; consequently, immunity induced by infections with other flaviviruses endemic to Brazil could potentially be responsible for the lack of ROCV infections. Herein, we evaluated the cross-protection mediated by other flaviviruses against ROCV infection using an experimental C57BL/6 mouse model. Cross-protection against ROCV infection was observed when animals had prior exposure to Ilheus virus or Saint Louis encephalitis virus, suggesting that cross-reactive anti-flavivirus antibodies may limit ROCV disease outbreaks.
Aims
Brazil ranks high in the number of coronavirus disease 19 (COVID‐19) cases and the COVID‐19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated ...conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID‐19. In order to follow biosafety recommendations, we used ultrasound‐guided minimally invasive autopsy (MIA‐US), and we present the results of 10 initial autopsies.
Methods and results
We used MIA‐US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis.
Conclusions
MIA‐US is safe and effective for the study of severe COVID‐19. Our findings show that COVID‐19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.
We investigated the mechanisms by which chronic administration of a multideficient diet after weaning alters bodily Na
+
handling, and culminates in high systolic blood pressure (SBP) at a juvenile ...age. From 28 to 92 days of age, weaned male Wistar rats were given a diet with low content and poor-quality protein, and low lipid, without vitamin supplementation, which mimics the diets consumed in impoverished regions worldwide. We measured food, energy and Na
+
ingestion, together with urinary Na
+
excretion, Na
+
density (Na
+
intake/energy intake), plasma Na
+
concentration, SBP, and renal proximal tubule Na
+
-transporting ATPases. Undernourished rats aged 92 days had only one-third of the control body mass, lower plasma albumin, higher SBP, higher energy intake, and higher positive Na
+
balance accompanied by decreased plasma Na
+
concentration. Losartan or Ang-(3–4) normalized SBP, and the combination of the 2 substances induced an accentuated negative Na
+
balance as a result of strong inhibition of Na
+
ingestion. Na
+
density in undernourished rats was higher than in control, irrespective of the treatment, and they had downregulated (Na
+
+K
+
)ATPase and upregulated Na
+
-ATPase in proximal tubule cells, which returned to control levels after Losartan or Ang-(3–4). We conclude that Na
+
density, not only Na
+
ingestion, plays a central role in the pathophysiology of elevated SBP in chronically undernourished rats. The observations that Losartan and Ang-(3–4) normalized SBP together with negative Na
+
balance give support to the proposal that Ang II⇒AT
1
R and Ang II⇒AT
2
R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.
•Systemic TNF-α increases carotid body afferent signalling to the brain.•TNF-α activates brain sympathetic networks and splanchnic sympathetic nerve activity.•Carotid body ablation blunts ...TNF-α-induced neuronal and sympathetic activation.•Ablation of carotid bodies or splanchnic nerves worsen TNF-α-induced inflammation.•Carotid body detects elevated TNF-α to trigger a sympathetic counteracting response.
Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we confirmed that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where many pre-sympathetic neurons reside. The activation of these neurons was accompanied by an increase in splanchnic sympathetic nerve activity. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF-α to activate a counteracting sympathetic anti-inflammatory mechanism.
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Gibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced ...toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these compounds against T. cruzi trypomastigotes and explore structure–activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups – ester and amide – and variating the substituent at the p-position in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 μM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 μM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results suggested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.
Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after ...fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions.
Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation.
HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05).
In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.
A large number of compiler optimizations are nowadays available to users. These optimizations interact with each other and with the input code in several and complex ways. The sequence of application ...of optimization passes can have a significant impact on the performance achieved. The effect of the optimizations is both platform and application dependent. The exhaustive exploration of all viable sequences of compiler optimizations for a given code fragment is not feasible. As this exploration is a complex and time-consuming task, several researchers have focused on Design Space Exploration (DSE) strategies both to select optimization sequences to improve the performance of each function of the application and to reduce the exploration time. In this article, we present a DSE scheme based on a clustering approach for grouping functions with similarities and exploration of a reduced search space resulting from the combination of optimizations previously suggested for the functions in each group. The identification of similarities between functions uses a data mining method that is applied to a symbolic code representation. The data mining process combines three algorithms to generate clusters: the Normalized Compression Distance, the Neighbor Joining, and a new ambiguity-based clustering algorithm. Our experiments for evaluating the effectiveness of the proposed approach address the exploration of optimization sequences in the context of the ReflectC compiler, considering 49 compilation passes while targeting a Xilinx MicroBlaze processor, and aiming at performance improvements for 51 functions and four applications. Experimental results reveal that the use of our clustering-based DSE approach achieves a significant reduction in the total exploration time of the search space (20× over a Genetic Algorithm approach) at the same time that considerable performance speedups (41% over the baseline) were obtained using the optimized codes. Additional experiments were performed considering the LLVM compiler, considering 124 compilation passes, and targeting a LEON3 processor. The results show that our approach achieved geometric mean speedups of 1.49 × , 1.32 × , and 1.24 × for the best 10, 20, and 30 functions, respectively, and a global improvement of 7% over the performance obtained when compiling with -O2.
The High‐Dynamic Double‐Crystal Monochromator (HD‐DCM) is a mechatronic system with unique control‐based architecture and deep paradigm changes as compared with traditional beamline monochromators. ...Aiming at unprecedented inter‐crystal positioning stability in vertical‐bounce double‐crystal monochromators (DCMs) of the order of 10 nrad RMS (1 Hz to 2.5 kHz), and not only in fixed‐energy but also in fly‐scan operation, it has been developed according to a `first‐time right' predictive design approach for hard X‐ray beamlines at Sirius, the fourth‐generation light source at the Brazilian Synchrotron Light Laboratory (LNLS/CNPEM). This work explores some of the challenges that emerge with this new technology and presents the latest commissioning results that demonstrate the unparallel performances of the HD‐DCM at the undulator‐based EMA (Extreme Methods of Analysis) beamline at Sirius. With the enabled fast spectroscopy fly‐scan possibilities, a new energy‐tuning evaluation method, based on wave‐propagation simulations, becomes part of a motion‐oriented analysis that is carried out to derive the multi‐axis non‐linear positioning problem, covering not only energy selection and fixed exit in the HD‐DCM but also the emission spectrum of an adjustable‐phase undulator (APU). The HD‐DCM control scheme and its flexible operation modes are described in detail as well. Furthermore, a new integration topology between the HD‐DCM and EMA's APU, coming already close to ultimate motion levels, is described and validated.
The High‐Dynamic Double‐Crystal Monochromator that has been developed for the fourth‐generation light source Sirius/LNLS is explored, with its unprecedented inter‐crystal stability performance around 10 nrad RMS both at fixed‐energy and continuous fly‐scan. Given the new paradigm and the unique enabling technology of its high‐performance mechatronic system, the engineering and operational aspects for the next‐level beamline experimental possibilities with a double‐crystal monochromator are comprehensively discussed. Fly‐scan spectroscopy scientific commissioning results are also presented.
Abstract As of August 2019, several oil slicks reached the Brazilian coast, compromising local ecosystems and the economy of coastal communities. In this context, this study aimed to assess seafood ...quality at the Canavieiras Extractive Reserve (RESEX), located in the state of Bahia, Northeastern Brazil, by determining polycyclic aromatic hydrocarbons (PAHs) concentrations in local biota following the oil spill. It was designed and carried out in a participatory manner, involving RESEX fishers, shellfish and crab gatherers and managers, as well as university researchers. A total of 72 biota samples were analyzed, and the sum of the 16 priority USEPA PAHs ranged from less than the limit of detection to 30.81 ng g-1 (w.w.). When also considering alkylated compounds, concentrations ranged from 3.53 to 360.75 ng g-1 (w.w.). No sample contained PAHs concentrations suggestive of human consumption risks. No difference in PAHs concentrations between the six studied areas and regarding different biota feeding habits were observed. Higher PAHs concentrations were generally noted in molluscs, as these organisms do not have enzyme systems capable of metabolizing these compounds. This initiative demonstrated the feasibility of participatory construction resulting in a study concerning valued species to local communities, ensuring a contribution to local fishing and marketing activities.
In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against ...clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against
Bacteroides fragilis
,
Bacteroides thetaiotaomicron
,
Bacteroides vulgatus
,
Bacteroides ovatus
,
Parabacteroides distasonis
and
Fusubacterium nucleatum
pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases. Some derivatives were even more active than the antimicrobial drugs secnidazole and metronidazole. Therefore, the compounds under study are suitable for in vivo evaluation and the microorganisms should be classified as susceptible to them. Electrochemical studies on the reduction of the nitro group revealed that the compounds show comparable reduction potentials, which are in the same range of the bio-reducible drugs secnidazole and benznidazole. The nitro group reduction potential is more favorable for the copper(II) complexes than for the starting ligands. Hence, the antimicrobial activities of the compounds under study might in part be related to intracellular bio-reduction activation. Considering the increasing resistance rates of anaerobic bacteria against a wide range of antimicrobial drugs, the present work constitutes an important contribution to the development of new antibacterial drug candidates.
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