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Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N -formyl peptide receptor (FPR) has been associated with inflammatory process. N -formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats ( Rattus norvegicus ) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/μL, 1 μL) followed by fMLP (1 mg/mL, 1 μL) or vehicle (VEH, saline 0.9%, 1 μL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine’s Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy. Graphical Abstract Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).

Status epilepticus (SE) is defined as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, mitochondrial dysfunction, oxidative stress, and energy failure. During SE, the neurons become overexcited, increasing energy consumption. Glucose uptake is increased via the sodium glucose cotransporter 1 (SGLT1) in the hippocampus under epileptic conditions. In addition, modulation of glucose can prevent neuronal damage caused by SE. Here, we evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity, and SGLT1 expression. Vehicle (VEH, saline 0.9%, 1 μL) or glucose (GLU; 1, 2 or 3 mM, 1 μL) were administered into hippocampus of male Wistar rats ( Rattus norvegicus ) before or after pilocarpine to induce SE. Behavioral analysis of seizures was performed for 90 min during SE. The memory and learning processes were analyzed by the inhibitory avoidance test. After 24 h of SE, neurodegeneration process, neuronal activity, and SGLT1 expression were evaluated in hippocampal and extrahippocampal regions. Modulation of hippocampal glucose did not protect memory dysfunction followed by SE. Our results showed that the administration of glucose after pilocarpine reduced the severity of seizures, as well as the number of limbic seizures. Similarly, glucose after SE reduced cell death and neuronal activity in hippocampus, subiculum , thalamus, amygdala, and cortical areas. Finally, glucose infusion elevated the SGLT1 expression in hippocampus. Taken together our data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes via an important support of SGLT1.

Intrahippocampal pilocarpine microinjection (H-PILO) induces status epilepticus (SE) that can lead to spontaneous recurrent seizures (SRS) and neurodegeneration in rodents. Studies using animal models have indicated that lectins mediate a variety of biological activities with neuronal benefits, especially galectin-1 (GAL-1), which has been identified as an effective neuroprotective compound. GAL-1 is associated with the regulation of cell adhesion, proliferation, programmed cell death, and immune responses, as well as attenuating neuroinflammation. Here, we administrated GAL-1 to Wistar rats and evaluated the severity of the SE, neurodegenerative and inflammatory patterns in the hippocampal formation. Administration of GAL-1 caused a reduction in the number of class 2 and 4 seizures, indicating a decrease in seizure severity. Furthermore, we observed a reduction in inflammation and neurodegeneration 24 h and 15 days after SE. Overall, these results suggest that GAL-1 has a neuroprotective effect in the early stage of epileptogenesis and provides new insights into the roles of exogenous lectins in temporal lobe epilepsy (TLE).

Transmission-blocking vaccines (TBVs) targeting sexual-stage antigens represent a critical tool for malaria control and elimination through inhibiting parasite development within mosquitoes. P230, displayed on the surface of gametocytes and gametes, plays a crucial role in gamete fertilization and is one of the leading TBV candidates for both Plasmodium falciparum and P. vivax. Antibodies induced by immunization with a recombinant P. falciparum protein encompassing a portion of N-terminal prodomain and domain 1 (Pfs230D1M) have revealed strong transmission-reducing activity (TRA) in preclinical studies. While a recombinant Pvs230D1, the P. vivax homolog of Pfs230D1M, has not been evaluated in preclinical immunogenicity studies, both Pfs230D1M and Pvs230D1 are currently scheduled for evaluation in clinical trials. In this study, we developed DNA vaccines encoding Pfs230D1M and Pvs230D1 for a side-by-side comparison of their immunogenicity. Potent antibody responses were induced in mice immunized with each DNA vaccine delivered by in vivo electroporation (EP). Anti-Pfs230D1M IgG exhibited potent dose-dependent TRA in a complement-dependent manner in standard membrane feeding assays (SMFA). In contrast, anti-Pvs230D1 IgG exhibited only moderate TRA in direct membrane feeding assay (DMFA) using blood from multiple P. vivax-infected donors. Antibodies induced by the Pfs230D1M DNA vaccine revealed a strong IgG1 bias and higher avidity as compared to a balanced IgG1/IgG2 response and lower antibody avidity by the Pvs230D1 DNA vaccine. Our results demonstrate the potential of both Pfs230D1M and Pvs230D1 DNA vaccines as TBV candidates against P. falciparum and P. vivax, and provide a rationale for future optimization to enhance the efficacy of DNA vaccines based on Pfs230 and Pvs230.

The purpose of this paper is to propose a framework for cybersecurity risk management in telemedicine. The framework, which uses a bow-tie approach for medical image diagnosis sharing, allows the identification, analysis, and assessment of risks, considering the ISO/TS 13131:2014 recommendations. The bow-tie method combines fault tree analysis (FTA) and event tree analysis (ETA). The literature review supported the identification of the main causes and forms of control associated with cybersecurity risks in telemedicine. The main finding of this paper is that it is possible, through a structured model, to manage risks and avoid losses for everyone involved in the process of exchanging medical image information through telemedicine services. Through the framework, those responsible for the telemedicine services can identify potential risks in cybersecurity and act preventively, recognizing the causes even as, in a mitigating way, identifying viable controls and prioritizing investments. Despite the existence of many studies on cybersecurity, the paper provides theoretical contributions to studies on cybersecurity risks and features a new methodological approach, which incorporates both causes and consequences of the incident scenario.

Circadian behavioral patterns in mosquitoes can be observed through their locomotor activity, which includes fundamental behaviors such as foraging, mating, and oviposition. These habits, which are fundamental to the life cycle of Anopheles mosquitoes, are closely related to pathogen transmission to humans. While rhythmic cycles of locomotor activity have been described in Anopheles species, no studies have been conducted on Anopheles darlingi species, the main malaria vector in the Amazon region. The aim of this study was to investigate how insemination status, blood meal, and Plasmodium vivax infection affect the locomotor activity of An. darlingi . The experiments were performed with 3- to 10-day-old An. darlingi females, which had been fed with 15% honey solution. These mosquitoes were obtained from the Malaria Vector Production and Infection Platform (PIVEM)/FIOCRUZ–RO. The experimental groups were divided into four categories: virgin vs. inseminated, unfed virgin vs. blood-fed virgin, unfed inseminated vs. blood-fed inseminated, and infected blood vs. uninfected blood. Locomotor activity was monitored using the Flybox equipment, capturing images that were subsequently converted into video to measure the insect activity, using PySoLo software. The periodicity and rhythmicity of mosquito locomotor activity were analyzed using MatLab® software. The locomotor activity of An. darlingi females showed a nocturnal and bimodal pattern under LD conditions. When comparing the insemination states and blood meal, there was a reduction in the locomotor activity in inseminated and blood-fed females. However, the P. vivax + infection did not increase locomotor activity of An. darlingi species.

The state of São Paulo, Brazil, where more than 94.000 dentists are currently registered, has become the epicenter of COVID-19 in Latin America. The aim of this cross-sectional study was to evaluate the impact of COVID-19 pandemic on dentists in this state. A semi-structured questionnaire was sent via e-mail to 93.280 dentists with active registration in the Dental Council of São Paulo (CROSP). The impact of COVID-19 pandemic was assessed through questions related to demographic, socioeconomic, dental practice characteristics and personal protective equipment (PPE) use. Ordinal logistic regression analysis was performed to investigate the association between all the variables (p<0.05). Over 8 days, 2113 responses were received. Only 26.52% of the sample reported a low-income reduction (from 0–10%), while the majority of dentists reported a more negative financial impact, 35.6% with a reduction of more than 50% of their monthly income. Dentists who worked in the private sector and at the capital had a greater financial impact when compared to those of the public sector and countryside of the state (p<0.05). Furthermore, about 83% reported not having received any specific training to control the transmission of coronavirus in the health area. This study provides evidence of the negative impact of the COVID-19 pandemic on the routine of dentists in the state of São Paulo, Brazil. Hopefully, this study will help dental and other health care professionals to better understand the consequences of disease in dental settings and strengthen preparedness throughout the dental health care system.

Anopheles darlingi mosquitoes are the main malaria vectors in the Amazon region and play a significant role in the high transmission cycle of Plasmodium vivax, particularly in areas undergoing degradation of the Amazon. Establishing an An. darlingi colony under laboratory conditions allows for critical studies on this vector, including insecticide resistance, vector competence, and the development of new tools for controlling vivax malaria. However, the establishment of mass-rearing mosquito colonies has proven challenging, with success being heavily dependent on supporting their reproduction. A key factor in this process is finding the most efficient blood source for feeding. Here, we evaluated the reproductive potential of An. darlingi using different blood feeding methods and sources. First, we assessed the effect of anesthesia on reproductive potential by comparing anesthetized mosquitoes with those that were physically restrained. Next, we assessed the best blood source using both direct and indirect blood feeding methods, the latter involving an artificial feeding system. The blood sources tested included from rabbits, chickens, mice, bovines, and humans. In the anesthesia tests, no significant differences in the evaluated biological parameters were observed between anesthetized or non-anesthetized groups. Similarly, no significant differences were detected in the biological parameters assessed for each blood source, regardless of whether the feeding was direct or indirect. Because all blood sources proved effective, the practicality of obtaining and maintaining blood becomes a crucial factor. In this regard, bovine blood emerged as an effective and practical alternative for maintaining an An. darlingi colony under laboratory conditions.

The majority of malaria cases in South America occur in rural areas of the Amazon region. Although these areas have a significant impact on malaria cases, few entomological studies have been carried out there. This study aimed to describe entomological parameters in settlements in Rondonia State, Brazil. Collections of anopheles were carried out using the Protected Human Attraction Technique (PHAT). The risk and the potential for malaria transmission were assessed using the human biting rate (HBR), the sporozoite rate (SR) and the entomological inoculation rate (EIR). The results confirmed that Nyssorhynchus darlingi is the predominant species in the two studied locations. Although settlement in the two study sites has occurred at different times, the species richness found was low, showing that environmental changes caused by anthropological actions have probably favor the adaptation of Ny. darlingi species. From the total of 615 anopheline mosquitoes assessed, seven (1.1%) were positive for Plasmodium sp. infections. The EIR revealed that Ny. darlingi contributes to malaria transmission in both locations, as it was responsible for 0.05 infectious bites in humans at night in the old settlement and 0.02 in the recent occupation. In the two study sites, the biting occurred more frequently at dusk. Nyssorhynchus darlingi was prevalent in areas of recent colonization but, even when present in a low density, this species could maintain the transmission of malaria in the older settlement. The entomological information obtained in this study is important and may aid the selection of vector control actions in these locations.

Background Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. Methods This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor ( FPR1 , FPR2 and FPR3 ) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Results ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p  = 0.0032; HAM/TSP, p  < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group ( p  = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals ( p  = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). Conclusions Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.