Reciprocal Inhibition and Coactivation of Ankle Muscles in Low- and High-Velocity Forward and Backward Perturbations.

Reciprocal inhibition and coactivation are strategies of the central nervous system used to perform various daily tasks. In automatic postural responses (APR), coactivation is widely investigated in the ankle joint muscles, however reciprocal inhibition, although clear in manipulative motor actions, has not been investigated in the context of APRs. The aim was to identify whether reciprocal inhibition can be observed as a strategy in the recruitment of gastrocnemius Medialis (GM), Soleus (So) and Tibialis Anterior (TA) muscles in low- and high-velocity forward and backward perturbations. We applied two balance perturbations with a low and a high velocity of displacement of the movable platform in forward and backward conditions and we evaluated the magnitude and latency time of TA, GM and So activation latency, measured by electromyography (EMG). In forward perturbations, coactivation of the three muscles was observed, with greater activation amplitude of the GM and lesser amplitude of the So and TA muscles. For backward, the pattern of response observed was activation of the TA muscle, a decrease in the EMG signal, which characterizes reciprocal inhibition of the GM muscle and maintenance of the basal state of the So muscle. This result indicates that backward perturbations are more challenging.

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Background: Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. Objectives: This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. Methods: By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. Results: The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. Conclusion: The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

Arabidopsis DNA glycosylase MBD4L improves recovery of aged seeds.

DNA glycosylases initiate the base excision repair (BER) pathway by catalyzing the removal of damaged or mismatched bases from DNA. The Arabidopsis DNA glycosylase methyl-CpG-binding domain protein 4 like (MBD4L) is a nuclear enzyme triggering BER in response to the genotoxic agents 5-fluorouracil and 5-bromouracil. To date, the involvement of MBD4L in plant physiological processes has not been analyzed. To address this, we studied the enzyme functions in seeds. We found that imbibition induced the MBD4L gene expression by generating two alternative transcripts, MBD4L.3 and MBD4L.4. Gene activation was stronger in aged than in non-aged seeds. Seeds from mbd4l-1 mutants displayed germination failures when maintained under control or ageing conditions, while 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 seeds reversed these phenotypes. Seed nuclear DNA repair, assessed by comet assays, was exacerbated in an MBD4L-dependent manner at 24 h post-imbibition. Under this condition, the BER genes ARP, APE1L, and LIG1 showed higher expression in 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 than in mbd4l-1 seeds, suggesting that these components could coordinate with MBD4L to repair damaged DNA bases in seeds. Interestingly, the ATM, ATR, BRCA1, RAD51, and WEE1 genes associated with the DNA damage response (DDR) pathway were activated in mbd4l-1, but not in 35S:MBD4L.3/mbd4l-1 or 35S:MBD4L.4/mbd4l-1 seeds. These results indicate that MBD4L is a key enzyme of a BER cascade that operates during seed imbibition, whose deficiency would cause genomic damage detected by DDR, generating a delay or reduction in germination.

Influence of acute heat shock on antioxidant defense of tropical fish, Psalidodon bifasciatus.

Psalidodon bifasciatus is a fish species sensitive to physical and chemical changes in water. It serves as a good bioindicator of temperature variations and is utilized in environmental monitoring studies in Brazilian rivers. The objective of this study was to evaluate antioxidant defense biomarkers in the heart, brain, and muscle of P. bifasciatus exposed to a 10 °C thermal increase. P. bifasciatus were collected and divided into a control group (21 °C) and groups subjected to thermal shock (31 °C) for periods of 2, 6, 12, 24, and 48h. Two-way ANOVA indicated that a 10 °C temperature increase caused oxidative stress in P. bifasciatus. This was evidenced by altered levels of lipid peroxidation (LPO), carbonylated proteins (PCO), and glutathione peroxidase (GPx) in the heart, catalase (CAT) and LPO in the brain, and LPO in the muscle. Principal component analysis (PCA) and integrated biomarker response (IBR) analysis indicated that, compared to the heart and muscle, the brain exhibited a greater activation of the antioxidant response. Sensitivity analysis indicated that the muscle was the most sensitive organ, followed by the brain and heart. Our results indicate that the stress response is tissue-specific through the activation of distinct mechanisms. These responses may be associated with the tissue's function as well as its energy demand. As expected, P. bifasciatus showed changes in response to thermal stress, with the brain showing the greatest alteration in antioxidant defenses and the muscle being the most sensitive tissue.

Effects of Resistance Exercise with and without Blood Flow Restriction on Acute Hemodynamic Responses: A Systematic Review and Meta-Analysis.

Low-load intensity resistance exercise with blood flow restriction (BFR) is an alternative method for enhancing strength and muscle mass. However, acute cardiovascular responses to a complete training session remain uncertain compared to high-load intensity resistance exercise (HI). Therefore, the objective of this study to examine acute and post-exercise hemodynamic responses to low-load BFR and HI protocols. This systematic review and meta-analysis (RD42022308697) followed PRISMA guidelines to investigate whether the responses of heart rate (HR), blood systolic (SBP), blood diastolic pressure (DBP), and rate pressure product (RPP) immediately after and up to 60 min post-exercise from BFR were consistent with those reported after resistance exercises performed at HI in healthy individuals. Searches using PICO descriptors were conducted in databases from January 2011 to December 2023, and effect sizes were determined by Hedge's g. The selected studies involved 160 participants in nine articles, for which the responses immediately after BFR and HI exercises showed no differences in HR (p = 0.23) or SBP (p = 0.57), but significantly higher DBP (p < 0.01) and lower RPP (p < 0.01) responses were found when comparing BFR to HI. Furthermore, the BFR and HI protocols showed no differences regarding SBP (p = 0.21) or DBP (p = 0.68) responses during a 15 to 60 min post-exercise period. Thus, these results indicated that hemodynamic responses are similar between BFR and HI, with a similar hypotensive effect up to 60 min following exercise.

Runway extinction in terrestrial toads (Rhinella arenarum): Instrumental or Pavlovian?

Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300 s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600 s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300 s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.

Linear mixed-effect models for correlated response to process electroencephalogram recordings.

A data set of clinical studies of electroencephalogram recordings (EEG) following data acquisition protocols in control individuals (Eyes Closed Wakefulness - Eyes Open Wakefulness, Hyperventilation, and Optostimulation) are quantified with information theory metrics, namely permutation Shanon entropy and permutation Lempel Ziv complexity, to identify functional changes. This work implement Linear mixed-effects models (LMEMs) for confirmatory hypothesis testing. The results show that EEGs have high variability for both metrics and there is a positive correlation between them. The mean of permutation Lempel-Ziv complexity and permutation Shanon entropy used simultaneously for each of the four states are distinguishable from each other. However, used separately, the differences between permutation Lempel-Ziv complexity or permutation Shanon entropy of some states were not statistically significant. This shows that the joint use of both metrics provides more information than the separate use of each of them. Despite their wide use in medicine, LMEMs have not been commonly applied to simultaneously model metrics that quantify EEG signals. Modeling EEGs using a model that characterizes more than one response variable and their possible correlations represents a new way of analyzing EEG data in neuroscience.

Method to determine instantaneous transient responses in pressurized pipes from transfer functions and state space for evaluation of leak signals.

This article addresses the impact of transient pressure anomalies in hydraulic systems, triggered by the opening or closing of valves or pumps, instantly disturbing the line of hydraulic gradient (LGH). This variation in pressure has significant consequences both in hydraulic and structural terms for water networks. Most of the existing techniques to detect transients in water distribution systems use asynchronous methods, generating timeless information that limits the response capacity in critical situations. Therefore, an automatic transient detection system based on the Internet of Things (IoT) is proposed, capable of identifying overpressure or underpressure pulses in soft real-time, activating alarms to facilitate decision-making. This approach helps maintain the safety of the water distribution system and prevent leaks in the network. Furthermore, a model of the transient behavior of pressure and flow is presented by linearizing the water hammer equations from the Laplace transform, thus generating a transfer function that describes the algebraic relationship between the outlet and inlet of the hydraulic system.•The transient analysis of the hydraulic system prototype underscores its high sensitivity to initial conditions, attributed to turbulence. This observation suggests the possible presence of a dynamic strange attractor related to water hammer phenomena in pressure pipes.•The methodology involving transfer functions and state-space models enables the assessment of how leaks impact the transient responses of the system, including the magnitude, duration, and frequency of disturbances generated by them.•The proposed method introduces a dynamic transfer function capable of identifying instantaneous changes over time in terms of flow and pressure.

Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Understanding desiccation tolerance and sex-specific responses in Bryum argenteum: insights from phenological phases and physiological analyses.

BACKGROUND AND AIMS: Desiccation tolerance (DT) is crucial for survival in arid environments, where organisms develop strategies in reproduction, maintenance and defence to cope with water scarcity. Therefore, investigating the relationship between reproduction and DT is essential to understand the ecology and adaptive strategies of species. This study explores the connection between the development of male and female gametangia in the moss Bryum argenteum and the decrease in DT during the progression of phenological phases in gametangia and protonema. METHODS: Samples collected from a dry tropical forest in Brazil were cultivated, cloned and subjected to desiccation. Subsequently, the physiological parameters of shoots and protonemata were analysed. Shoot and protonema regeneration were monitored for 28 d after the physiological analyses. Both phases were subjected to control and desiccation treatments. KEY RESULTS: Significant effects of desiccation and sex on the physiological parameters and regeneration capacity of shoots and protonemata were found. Male shoots generally exhibited lower values of Fv/Fm (quantum efficiency of photosystem II) and ϕPSII (effective quantum yield of photosystem II), while females demonstrated higher values and better recovery after desiccation. Protonemata also showed variation in Fv/Fm over time and with sex, with no significant differences in ϕPSII between them. Desiccated male shoots had higher mortality rates and produced fewer new shoots. For females, the regeneration patterns varied between the desiccation-exposed groups and the control, with decreased shoot production, and some protonemata growing into filaments without forming shoots. CONCLUSION: These findings improve our understanding of the ecological responses of bryophytes to desiccation stress and provide insights into their adaptive strategies in challenging environments, such as the possible rarity of males in dioicous moss populations.

Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses.

Parasites possess remarkable abilities to evade and manipulate the immune response of their hosts. Echinococcus granulosus is a parasitic tapeworm that causes cystic echinococcosis in animals and humans. The hydatid fluid released by the parasite is known to contain various immunomodulatory components that manipulate host´s defense mechanism. In this study, we focused on understanding the effect of hydatid fluid on dendritic cells and its impact on autophagy induction and subsequent T cell responses. Initially, we observed a marked downregulation of two C-type lectin receptors in the cell membrane, CLEC9A and CD205 and an increase in lysosomal activity, suggesting an active cellular response to hydatid fluid. Subsequently, we visualized ultrastructural changes in stimulated dendritic cells, revealing the presence of macroautophagy, characterized by the formation of autophagosomes, phagophores, and phagolysosomes in the cell cytoplasm. To further elucidate the underlying molecular mechanisms involved in hydatid fluid-induced autophagy, we analyzed the expression of autophagy-related genes in stimulated dendritic cells. Our results demonstrated a significant upregulation of beclin-1, atg16l1 and atg12, indicating the induction of autophagy machinery in response to hydatid fluid exposure. Additionally, using confocal microscopy, we observed an accumulation of LC3 in dendritic cell autophagosomes, confirming the activation of this catabolic pathway associated with antigen presentation. Finally, to evaluate the functional consequences of hydatid fluid-induced autophagy in DCs, we evaluated cytokine transcription in the splenocytes. Remarkably, a robust polyfunctional T cell response, with inhibition of Th2 profile, is characterized by an increase in the expression of il-6, il-10, il-12, tnf-α, ifn-γ and tgf-ß genes. These findings suggest that hydatid fluid-induced autophagy in dendritic cells plays a crucial role in shaping the subsequent T cell responses, which is important for a better understanding of host-parasite interactions in cystic echinococcosis.

How Professional and Market Logics and the Conflict between Institutional Demands Affect Hospital Accreditation Compliance: A Multiple-Case Study in Brazil.

Hospital accreditation has become ubiquitous in developing countries. While research acknowledges that accreditation can enhance healthcare quality, efficiency, and safety, concerns persist regarding hospitals' management of conflicts stemming from the diverse institutional logic inherent in this process. Therefore, this study aimed to investigate how professional and market logic, alongside conflicts arising from institutional demands, affect compliance with hospital accreditation. To this end, we conducted a multiple-case study in four Brazilian hospitals employing in-depth interviews and on-site observations. The triangulation of narrative analysis and the outcomes of multiple correspondence analysis revealed that when professional logic predominates, there is a greater propensity to tailor accredited activities by segmenting the tasks between physicians and nurses with the intention of mitigating existing conflicts. Conversely, when conflicts occur over established goals between professionals and orientated marked logic executives, the accreditation process is impeded, resulting in non-compliance. Ultimately, the findings underscore the alignment between the pursuit of legitimacy and efficiency within the accreditation process. We conclude by delineating the theoretical and practical implications of scrutinizing the internal dynamics of institutional logic.

Nine-Month Trend of IgG Antibody Persistence and Associated Symptoms Post-SARS-CoV-2 Infection.

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

Perkinsus spp. Occurrence in South America: A review.

Marine mollusk production is increasing worldwide, and this trend is being evidenced in South American countries, where several species of bivalves are produced, exploited, and traded. This activity brings benefits either for the ecosystem, as it is a less impactful and polluting than other aquaculture practices, and to coastal human communities, as it provides food and income. However, emergence of outbreaks by pathogens is a major concern and can put an entire developing sector at risk. Perkinsosis is a disease caused by Perkinsus spp. protozoans that affect mollusks worldwide. In this review we provide information on Perkinsus spp. among bivalves from South America. Infections by these parasites were only reported to date among coastal Atlantic bivalves of Argentina, Uruguay, and Brazil. The vast majority of cases and studies are reported from Brazil. We comprehensively review those results here. Finally, we suggest some considerations for future investigations that may expand our knowledge of these parasites.

Maternal and neonatal effects of epidural levobupivacaine combined with fentanyl or sufentanil for elective cesarean-section in brachycephalic breeds.

The aim of this study was to compare the safety and clinical efficacy of epidural levobupivacaine combined with fentanyl or sufentanil for bitches undergoing elective cesarean-section and the impact of these anesthetic protocols on neonatal viability. The anesthetic protocol consisted of intramuscular morphine (0.2 mg/kg), followed by an intravenous bolus of propofol, in a dose sufficient to allowed the puncture of the lumbosacral space. The dogs were randomly allocated to receive 0.5 % levobupivacaine plus fentanyl (2.5 µg/kg; LF: n = 9) or sufentanil (1 µg/kg; LS; n = 11). Maternal cardiorespiratory parameters were monitored at specific time points during surgery. Intraoperative propofol supplementation was based on the presence of head and/or thoracic limb movements. Neonatal reflex responses and the Apgar score (range 0-10 points) were assessed at 5 and 60 minutes after birth. Puppy mortality rate was recorded until 24 hours after birth. Data were analyzed using two-way ANOVA, Tukey's test, Wilcoxon signed rank test, and Fisher's exact test (P < 0.05). Intraoperatively, maternal cardiorespiratory variables and propofol requirements were similar between groups, with no detection of anesthetic complications. The puppy reflex responses did not differ between groups at any time point. The medians (range) of Apgar scores were lower (P = 0.016) in the LF [5 (1-9)] at 5 minutes in comparison with LS [6 (2-9)], while no intergroup differences were recorded at 60 minutes [LF = 8 (2-10); LS = 9 (6-10]. The total mortality rate was 4.1 %. In the LS group, no puppies died, while in the LF 8 % of the puppies died in the first 24 hours after birth (P = 0.11). Epidural levobupivacaine combined with fentanyl or sufentanil provided minimal maternal and neonatal adverse effects, but neither protocol enabled the performance of a C-section in 100 % of the French and English bulldogs, without propofol supplementation.

Differential photosynthetic plasticity of Amazonian tree species in response to light environments.

To investigate how and to what extent there are differences in the photosynthetic plasticity of trees in response to different light environments, six species from three successional groups (late successional, mid-successional, and pioneers) were exposed to three different light environments [deep shade - DS (5% full sunlight - FS), moderate shade - MS (35% FS) and full sunlight - FS]. Maximum net photosynthesis (Amax), leaf N partitioning, stomatal, mesophile, and biochemical limitations (SL, ML, and BL, respectively), carboxylation velocity (Vcmax), and electron transport (Jmax) rates, and the state of photosynthetic induction (IS) were evaluated. Higher values of Amax, Vcmax, and Jmax in FS were observed for pioneer species, which invested the largest amount of leaf N in Rubisco. The lower IS for pioneer species reveals its reduced ability to take advantage of sunflecks. In general, the main photosynthetic limitations are diffusive, with SL and ML having equal importance under FS, and ML decreasing along with irradiance. The leaf traits, which are more determinant of the photosynthetic process, respond independently in relation to the successional group, especially with low light availability. An effective partitioning of leaf N between photosynthetic and structural components played a crucial role in the acclimation process and determined the increase or decrease of photosynthesis in response to the light conditions.

Threat directionality modulates defensive reactions in humans: cardiac and electrodermal responses.

Features of threatening cues and the associated context influence the perceived imminence of threat and the defensive responses evoked. To provide additional knowledge about how the directionality of a threat (i.e. directed-towards or away from the viewer) might impact defensive responses in humans, participants were shown pictures of a man carrying a gun (threat) or nonlethal object (neutral) directed-away from or towards the participant. Cardiac and electrodermal responses were collected. Compared to neutral images, threatening images depicting a gun directed-towards the participant induced sustained bradycardia and an increased electrodermal response, interpreted as immobility under attack. This defensive immobility reaction is evoked by high perceived threat and inescapable situations and indicates intense action preparation. Pictures of guns directed-away from the participant induced shorter bradycardia and no significant modulation of the electrodermal response compared to neutral pictures, which might be consistent with the perception of a less threatening situation. The results show that the directionality of threat stimuli is a key factor that prompts different patterns of defensive responses.

Assessing the Match Physical Responses of International Referees for Footballers with Cerebral Palsy: A Tournaments and Halves Comparative Analysis.

Similar to conventional football, the modality dedicated to footballers with cerebral palsy (CP) requires referees who cope with the physical demands imposed during competitive matches to apply the rules of the game. While a significant body of research has explored the physical demands on referees in mainstream football, there is a noticeable lack of data regarding CP football. This study aimed to examine the physical response of international referees participating in different levels of world competitions for footballers with CP. Thirteen international referees, who officiated 49 matches in the men's 2022 World Cup (1st to 15th ranked teams) and 2022 World Championships (16th to 30th ranked teams), participated in this study. A cross-sectional design was used to determine the physical responses and compare the 1st and 2nd halves and the performance in the different tournaments, recording physical variables throughout the matches. Significant higher physical responses were observed in the World Cup in comparison to the World Championship. Overall, high-level tournaments have been shown to elicit more intense physical responses from referees officiating CP football matches compared to lower-level tournaments. For the World Cup, a significantly higher number of accelerations and decelerations were registered in the 1st half compared to the 2nd half. This information may be useful for the strength and conditioning coaches of referees to plan weekly training sessions more specifically and adjust the periodical training load and post-match recovery protocols.

Oxidative stress and neurotoxicity induced by exposure to settleable atmospheric particulate matter in bullfrog tadpoles, Aquarana catesbeiana, (Shaw, 1802).

Bullfrog tadpoles, Aquarana catesbeiana, were exposed to settleable particulate matter (SePM), (1 g L-1, 96 h) and their organs were collected for analysis of metal/metalloid, oxidative stress and neurotoxicity in liver, muscle, kidney and brain. The SePM water of the exposed groups contained 18 of the 28 metals/metalloids detected in ambient particulate matter (APM). Fe56 and Al were those that presented the highest concentrations, Cr, Mn, Pb and Cu increased from 10 to 20 times and Ti, V, Sr, Rb, Cd, Sn and Ni increased from 1 to 3 times compared to the control. Bioaccumulation of metals/metalloids in the exposure water varied significantly between organs, with the muscle and liver showing the highest concentrations of metals, followed by the brain. Lipoperoxidation and malondialdehyde increased only in muscle, while carbonyl proteins increased only in the liver and brain. Regarding nitric oxide synthase, there was an increase in the liver and brain in the group exposed to SePM. Catalase activity decreased in the liver and muscle, while the activity of glutathione peroxidase, increased in the liver and kidney and decreased in muscle. Glutathione S-transferase, which is mainly responsible for detoxification, increased in the liver and decreased in muscle and the kidney. Cholinesterase activity increased only in the muscle. The results indicate oxidative stress, due to oxidation catalyzed by metals, components of SePM. Thus, the results contribute to the understanding that SePM has a deleterious effect on the aquatic environment, negatively affecting bullfrog tadpoles, in different ways and levels in relation to the analyzed organs.

Blocking the CTLA-4 and PD-1 pathways during pulmonary paracoccidioidomycosis improves immunity, reduces disease severity, and increases the survival of infected mice.

Immune checkpoint pathways, i.e., coinhibitory pathways expressed as feedback following immune activation, are crucial for controlling an excessive immune response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) are the central classical checkpoint inhibitory (CPI) molecules used for the control of neoplasms and some infectious diseases, including some fungal infections. As the immunosuppression of severe paracoccidioidomycosis (PCM), a chronic granulomatous fungal disease, was shown to be associated with the expression of coinhibitory molecules, we hypothesized that the inhibition of CTLA-4 and PD-1 could have a beneficial effect on pulmonary PCM. To this end, C57BL/6 mice were infected with Paracoccidioides brasiliensis yeasts and treated with monoclonal antibodies (mAbs) α-CTLA-4, α-PD-1, control IgG, or PBS. We verified that blockade of CTLA-4 and PD-1 reduced the fungal load in the lungs and fungal dissemination to the liver and spleen and decreased the size of pulmonary lesions, resulting in increased survival of mice. Compared with PBS-treated infected mice, significantly increased levels of many pro- and anti-inflammatory cytokines were observed in the lungs of α-CTLA-4-treated mice, but a drastic reduction in the liver was observed following PD-1 blockade. In the lungs of α-CPI and IgG-treated mice, there were no changes in the frequency of inflammatory leukocytes, but a significant reduction in the total number of these cells was observed. Compared with PBS-treated controls, α-CPI- and IgG-treated mice exhibited reduced pulmonary infiltration of several myeloid cell subpopulations and decreased expression of costimulatory molecules. In addition, a decreased number of CD4+ and CD8+ T cells but sustained numbers of Th1, Th2, and Th17 T cells were detected. An expressive reduction in several Treg subpopulations and their maturation and suppressive molecules, in addition to reduced numbers of Treg, TCD4+, and TCD8+ cells expressing costimulatory and coinhibitory molecules of immunity, were also detected. The novel cellular and humoral profiles established in the lungs of α-CTLA-4 and α-PD-1-treated mice but not in control IgG-treated mice were more efficient at controlling fungal growth and dissemination without causing increased tissue pathology due to excessive inflammation. This is the first study demonstrating the efficacy of CPI blockade in the treatment of pulmonary PCM, and further studies combining the use of immunotherapy with antifungal drugs are encouraged.