Dioclea violacea lectin has potent in vitro leishmanicidal activity against Leishmania infantum via carbohydrate recognition domain.

Despite promising advancements in leishmaniasis treatment, existing therapies often face limitations and significant side effects, stimulating the search for novel therapeutic alternatives. In this context, lectins, such as DVL extracted from Dioclea violacea seeds, have emerged as potential candidates due to their diverse biological activities. This study represents the first investigation of the leishmanicidal potential of DVL in vitro against Leishmania infantum. Our results demonstrate that DVL exhibits a leishmanicidal effect (IC50/24 h = 49.37 µg/mL or 2 µM), binding to glycans on L. infantum. Fluorescence assays revealed that DVL can induce the production of reactive oxygen species (ROS) and cause damage to the parasite's membrane. DVL demonstrated a modulating effect when combined with amphotericin B and glucantime, enhancing the activity of these drugs by 40 % and 80 %, respectively. It also showed no cytotoxicity in Raw 264.7 cells and was able to override the toxic effect of amphotericin B on cells and reduce the survival rate of macrophages infected with amastigote forms, as well as their percentage of infection by 31 %. Therefore, DVL shows promise as a treatment for visceral leishmaniasis caused by L. infantum. Our findings provide valuable insights for future therapeutic development targeting leishmania glycans.

Occurrence of coccidioidomycosis in a tertiary hospital in the Brazilian semi-arid region: diagnostic challenges.

Coccidioidomycosis is a systemic fungal infection that primarily affects the lungs in mammals. It is endemic to certain areas of the Americas. In Brazil, the disease occurs exclusively in the Northeast of the country, and the only etiological agent described is Coccidioides posadasii, typically found in the soil of arid regions with low rainfall. Given the scarcity of cases in Brazil, a descriptive study was conducted based on cases diagnosed with coccidioidomycosis between 2012 and 2022 at a tertiary hospital in the northeastern region of Brazil. The study analyzed medical records to identify cases of coccidioidomycosis diagnosed by clinical and/or laboratory data, discussing their clinical-epidemiological aspects. Thirteen patients were identified from seven municipalities in Ceará, all of whom were male, with a mean age of 19 years. The main risk factor was armadillo hunting, and the clinical manifestations included cough, fever, and chest pain. In this study, two patients were diagnosed by serology, one by microscopy, and ten suspected cases were diagnosed based on the clinical and epidemiological picture. Twelve patients were treated with antifungals. Clinical improvement with hospital discharge occurred in twelve patients, while one patient died. The data corroborate information from the scientific literature that the area covered by the referral hospital is endemic for coccidioidomycosis. However, local resources for diagnosing this disease were found to be deficient, with a high rate of presumptive diagnoses. This study highlights the need for actions by health surveillance systems and greater efficiency in diagnosing coccidioidomycosis in endemic areas of Brazil.

Analysis of environmental variables and deforestation in the amazon using logistical regression models.

In this study, we applied a multivariate logistic regression model to identify deforested areas and evaluate the current effects on environmental variables in the Brazilian state of Rondônia, located in the southwestern Amazon region using data from the MODIS/Terra sensor. The variables albedo, temperature, evapotranspiration, vegetation index, and gross primary productivity were analyzed from 2000 to 2022, with surface type data from the PRODES project as the dependent variable. The accuracy of the models was evaluated by the parameters area under the curve (AUC), pseudo R2, and Akaike information criterion, in addition to statistical tests. The results indicated that deforested areas had higher albedo (25%) and higher surface temperatures (3.2 °C) compared to forested areas. There was a significant reduction of the EVI (16%), indicating water stress, and a decrease in GPP (18%) and ETr (23%) due to the loss of plant biomass. The most precise model (91.6%) included only surface temperature and albedo, providing important information about the environmental impacts of deforestation in humid tropical regions.

HuBar: A Visual Analytics Tool to Explore Human Behavior based on fNIRS in AR Guidance Systems.

The concept of an intelligent augmented reality (AR) assistant has significant, wide-ranging applications, with potential uses in medicine, military, and mechanics domains. Such an assistant must be able to perceive the environment and actions, reason about the environment state in relation to a given task, and seamlessly interact with the task performer. These interactions typically involve an AR headset equipped with sensors which capture video, audio, and haptic feedback. Previous works have sought to facilitate the development of intelligent AR assistants by visualizing these sensor data streams in conjunction with the assistant's perception and reasoning model outputs. However, existing visual analytics systems do not focus on user modeling or include biometric data, and are only capable of visualizing a single task session for a single performer at a time. Moreover, they typically assume a task involves linear progression from one step to the next. We propose a visual analytics system that allows users to compare performance during multiple task sessions, focusing on non-linear tasks where different step sequences can lead to success. In particular, we design visualizations for understanding user behavior through functional near-infrared spectroscopy (fNIRS) data as a proxy for perception, attention, and memory as well as corresponding motion data (acceleration, angular velocity, and gaze). We distill these insights into embedding representations that allow users to easily select groups of sessions with similar behaviors. We provide two case studies that demonstrate how to use these visualizations to gain insights about task performance using data collected during helicopter copilot training tasks. Finally, we evaluate our approach by conducting an in-depth examination of a think-aloud experiment with five domain experts.

TopoMap++: A faster and more space efficient technique to compute projections with topological guarantees.

High-dimensional data, characterized by many features, can be difficult to visualize effectively. Dimensionality reduction techniques, such as PCA, UMAP, and t-SNE, address this challenge by projecting the data into a lower-dimensional space while preserving important relationships. TopoMap is another technique that excels at preserving the underlying structure of the data, leading to interpretable visualizations. In particular, TopoMap maps the high-dimensional data into a visual space, guaranteeing that the 0-dimensional persistence diagram of the Rips filtration of the visual space matches the one from the high-dimensional data. However, the original TopoMap algorithm can be slow and its layout can be too sparse for large and complex datasets. In this paper, we propose three improvements to TopoMap: 1) a more space-efficient layout, 2) a significantly faster implementation, and 3) a novel TreeMap-based representation that makes use of the topological hierarchy to aid the exploration of the projections. These advancements make TopoMap, now referred to as TopoMap++, a more powerful tool for visualizing high-dimensional data which we demonstrate through different use case scenarios.

Copaifera spp. oleoresins control Trypanosoma cruzi infection in human trophoblast cells (BeWo) and placental explants.

Congenital Chagas disease (CCD) is a worldwide neglected problem with significant treatment limitations. This study aimed to evaluate the potential of Copaifera spp. oleoresins (ORs) against Trypanosoma cruzi infection in trophoblast cells (BeWo lineage) and human chorionic villous explants (HCVE). The cytotoxicity of ORs was investigated using LDH and MTT assays. T. cruzi (Y strain) proliferation, invasion and reversibility were assessed in OR-treated BeWo cells, and proliferation was evaluated in OR-treated HCVE. The ultrastructure of T. cruzi trypomastigotes and amastigotes treated with ORs were analyzed by scanning and transmission electronic microscopy. ROS production in infected and treated BeWo cells and cytokines in BeWo and HCVE were measured. The ORs irreversibly decreased T. cruzi invasion, proliferation and release in BeWo cells by up to 70 %, 82 % and 80 %, respectively, and reduced parasite load in HCVE by up to 80 %. Significant structural changes in treated parasites were observed. ORs showed antioxidant capacity in BeWo cells, reducing ROS production induced by T. cruzi infection. Also, T. cruzi infection modulated the cytokine profile in both BeWo cells and HCVE; however, treatment with ORs upregulated cytokines decreased by T. cruzi infection in BeWo cells, while downregulated cytokines increased by the T. cruzi infection in HCVE. In conclusion, non-cytotoxic concentrations of Copaifera ORs demonstrated promising potential for controlling T. cruzi infection in models of the human maternal-fetal interface.

Relación densidad septo-ventrículo izquierdo como parámetro de detección de anemia en tomografía computarizada no contrastada de tórax en observadores con entrenamiento básico / Septum-Left Ventricular Density Ratio as a Parameter for Detecting Anemia in Non-Contrasted Chest Computed Tomography in Observers with Basic Training

Introducción: La anemia es frecuentemente subdiagnosticada dada su vaga sintomatología. Estudios con evaluación subjetiva-visual por expertos describen signos tomográficos sugerentes de anemia, tales como el septo denso. Proponemos que lectores con entrenamiento básico realicen mediciones objetivas de alto poder estadístico para la detección de anemia. Material y Métodos: Se cruzaron datos de tomografía computarizada (TC) de tórax no contrastada (2021) con medición de hemoglobina plasmática (Hb) realizada 24 horas antes o después del estudio tomográfico. Dos estudiantes de Medicina, previamente entrenados, realizaron mediciones de Unidades Hounsfield (UH) en el septo interventri-cular (SIV) y cavidades ventriculares derecho (VD) e izquierdo (VI). Las relaciones SIV/VI y SIV/VD se correlacionaron con los valores de Hb. Se analizó la variabilidad interob-servador y se determinó el punto de corte óptimo para detectar anemia. Resultados: En una muestra de 112 casos, hubo alta concordancia interobservador con r de 0,85 (VD), 0,67 (SIV) y 0,87 (VI). La relación SIV/VI obtuvo el mayor AUC con 0,86 (IC 95%: 0,72 a 0,91), con una sensibilidad de 80% y especificidad de 88% utilizando un punto de corte de 1,15. Conclusiones: La razón SIV/VI con punto de corte de 1,15 es un parámetro confiable para detectar anemia mediante TC de tórax no contrastada, en observadores con entrenamiento básico.

Introduction: Anemia is frequently underdiagnosed given its vague symptomatology. Studies with subjective-visual evaluation by experts describe tomographic signs suggestive of anemia, such as a dense septum. This study aims to evaluate if readers with basic training can perform high statistical value measurements for anemia detection. Material and Methods: Data of non-contrast thoracic computed tomography (CT) (2021) with a measurement of plasma hemoglobin (Hb) performed 24 hours before or after the CT were identified. Two previously trained medical students performed measurements of Hounsfield Units (HU) on the interventricular septum (IVS) and right (RV) and left (LV) ventricular cavities. The SIV/VI and SIV/VD ratios were correlated with Hb values. Interobserver variability was analyzed and the optimal cut-off point to detect anemia was determined. Results: In a sample of 112 cases, there was a high interobserver correlation with r of 0.85 (VD), 0.67 (SIV), and 0.87 (VI). SIV/VI ratio obtained the highest AUC with 0.86 (95% CI: 0.72 to 0.91), with a sensitivity of 80% and specificity of 88% using a cut-off point of 1.15. Conclusions: The SIV/VI ratio with a cut-off point of 1.15 is a reliable parameter to detect anemia using non-contrast chest CT in observers with basic training.

Patients recovering from COVID-19 who presented with anosmia during their acute episode have behavioral, functional, and structural brain alterations.

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.

Analysis of parental origin of de novo pathogenic CNVs in patients with intellectual disability.

Chromosomal Microarray Analysis (CMA) has increased the comprehension of the mechanisms of copy number variation (CNV) formation, classification of these rearrangements, type of recurrence, and its origin, and has also been a powerful approach to identifying CNVs in individuals with intellectual disability. The aim of this study was to establish the parental origin of de novo pathogenic CNV in a cohort of patients with intellectual disability from the public health system of Goiás-Brazil. CMA was done in 76 trios and we identified 15 de novo pathogenic CNVs in 12 patients with intellectual disability. In a total of 15 de novo pathogenic CNV, 60% were derived from the maternal germline and 40% from the paternal germline. CNV flanked by low copy repeats (LCR) were identified in 46.7% and most of them were of maternal origin. No significant association was observed between paternal age and the mutation rate of de novo CNVs. The presence of high-identity LCRs increases the occurrence of CNV formation mediated by non-allelic homologous recombination and the majority of paternal CNVs are non-recurrent. The mechanism of formation of these CNV may have been by microhomology-mediated break-induced replication or non-homologous end joining.

The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Concanavalin A, lectin from Canavalia ensiformis seeds has Leishmania infantum antipromastigote activity mediated by carbohydrate recognition domain.

Leishmaniases, caused by Leishmania parasites, are widespread and pose significant health risks globally. Visceral leishmaniasis (VL) is particularly prevalent in Brazil, with high morbidity and mortality rates. Traditional treatments, such as pentavalent antimonials, have limitations due to toxicity and resistance. Therefore, exploring new compounds like lectins is crucial. Concanavalin A (ConA) has shown promise in inhibiting Leishmania growth. This study aimed to evaluate its leishmanicidal effect on L. infantum promastigotes and understand its mechanism of action. In vitro tests demonstrated inhibition of promastigote growth when treated with ConA, with IC50 values ranging from 3 to 5 µM over 24-72 h. This study suggests that ConA interacts with L. infantum glycans. Additionally, ConA caused damage to the membrane integrity of parasites and induced ROS production, contributing to parasite death. Scanning electron microscopy confirmed morphological alterations in treated promastigotes. ConA combined with the amphotericin B (AmB) showed synergistic effects, reducing the required dose of AmB, and potentially mitigating its toxicity. ConA demonstrated no cytotoxic effects on macrophages, instead stimulating their proliferation. These findings reinforce that lectin exhibits promising leishmanicidal activity against L. infantum promastigotes, making ConA a potential candidate for leishmaniasis treatment.

Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases.

Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1-Vps34 complexes involved in autophagy and protein sorting. In T. cruzi epimastigotes, (a non-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that T. cruzi Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.

MOUNTAINEER: Topology-Driven Visual Analytics for Comparing Local Explanations.

With the increasing use of black-box Machine Learning (ML) techniques in critical applications, there is a growing demand for methods that can provide transparency and accountability for model predictions. As a result, a large number of local explainability methods for black-box models have been developed and popularized. However, machine learning explanations are still hard to evaluate and compare due to the high dimensionality, heterogeneous representations, varying scales, and stochastic nature of some of these methods. Topological Data Analysis (TDA) can be an effective method in this domain since it can be used to transform attributions into uniform graph representations, providing a common ground for comparison across different explanation methods. We present a novel topology-driven visual analytics tool, Mountaineer, that allows ML practitioners to interactively analyze and compare these representations by linking the topological graphs back to the original data distribution, model predictions, and feature attributions. Mountaineer facilitates rapid and iterative exploration of ML explanations, enabling experts to gain deeper insights into the explanation techniques, understand the underlying data distributions, and thus reach well-founded conclusions about model behavior. Furthermore, we demonstrate the utility of Mountaineer through two case studies using real-world data. In the first, we show how Mountaineer enabled us to compare black-box ML explanations and discern regions of and causes of disagreements between different explanations. In the second, we demonstrate how the tool can be used to compare and understand ML models themselves. Finally, we conducted interviews with three industry experts to help us evaluate our work.

Two in ten patients seeking addiction treatment within São Paulo's Crackland report recent use of Synthetic Cannabinoids.

The profile investigation of crack cocaine dependents seeking addiction treatment within Sao Paulo's open drug use scene known as "Crackland" demonstrated that 20% of them reported consuming variations of Synthetic Cannabinoids. This equated to 1.054 patients in a span of four months (between 08/05/2023 to 08/09/2023). This preliminary finding is well-timed and holds significant value making it suitable for a briefer publication format, such as a letter, that can promptly disseminate this relevant information to the scientific community. Additional and complementary evidence expanding the discussion beyond the medical aspects of SC consumption is also provided. This figure is a clear indication of the shift in the population accessing this drug, now reaching the most vulnerable segment of our nation's population. The letter brings on further insights with a more social perspective, also discussing the intricate interplay between affordability, availability price and how criminal organizations are likely involved now with SC's control and distribution in Brazil.

Coupling of Modes in Step-Index Plastic Optical Fibers by Using D-Shape Technique.

This article presents a technique for reducing the stabilization length of steady-state modes in step-index plastic optical fibers (POFs), which is significant for sensor networks, Internet of Things, signal processing, and data fusion in sensor systems. The results obtained with the com- putational tool developed suggest that the D-shape created in the POF effectively reduces the stabi- lization length of the modes and, by extension, minimizes the dispersion effects of the modes by filtering out high-order modes. Applying the analysis to commercial POFs, the authors experimen- tally verified a reduction in the stabilization length of modes from 27 to 10 m and from 20 m to 5 m. Reducing the mode stabilization length minimizes the bit error rate (BER) in short-length SI-POF- based optical links operating at 250 Mbp/s. A reduction from 7.6 × 10-7 to 3.7 × 10-10 was achieved.

Few-shot genes selection: subset of PAM50 genes for breast cancer subtypes classification.

BACKGROUND: In recent years, researchers have made significant strides in understanding the heterogeneity of breast cancer and its various subtypes. However, the wealth of genomic and proteomic data available today necessitates efficient frameworks, instruments, and computational tools for meaningful analysis. Despite its success as a prognostic tool, the PAM50 gene signature's reliance on many genes presents challenges in terms of cost and complexity. Consequently, there is a need for more efficient methods to classify breast cancer subtypes using a reduced gene set accurately. RESULTS: This study explores the potential of achieving precise breast cancer subtype categorization using a reduced gene set derived from the PAM50 gene signature. By employing a "Few-Shot Genes Selection" method, we randomly select smaller subsets from PAM50 and evaluate their performance using metrics and a linear model, specifically the Support Vector Machine (SVM) classifier. In addition, we aim to assess whether a more compact gene set can maintain performance while simplifying the classification process. Our findings demonstrate that certain reduced gene subsets can perform comparable or superior to the full PAM50 gene signature. CONCLUSIONS: The identified gene subsets, with 36 genes, have the potential to contribute to the development of more cost-effective and streamlined diagnostic tools in breast cancer research and clinical settings.

Self-reported bruxism in patients with post-traumatic stress disorder.

OBJECTIVE: The present study aimed to investigate the association between self-reported awake/sleep bruxism, and orofacial pain with post-traumatic stress disorder (PTSD). METHODS: A case-control study with a convenience sample was designed. Participants were recruited from a university-based Trauma Ambulatory. The diagnosis of PTSD was established through a clinical interview and the Structured Clinical Interview (SCID-I/P). Thirty-eight PTSD patients and 38 controls completed the Research Diagnostic Criteria for Temporomandibular Disorders Axis-II to categorize awake/sleep bruxism and orofacial pain. Following this, we performed a short clinical examination of the temporomandibular joint and extraoral muscles. RESULTS: Adjusted logistic regression analysis showed that awake bruxism was associated with PTSD (OR = 3.38, 95% CI = 1.01-11.27, p = 0.047). Sleep bruxism was not associated with any covariate included in the model. In a Poisson regression model, PTSD (IRR = 3.01, 95% CI = 1.38-6.55, p = 0.005) and the muscle pain/discomfort (IRR = 5.12, 95% CI = 2.80-9.36, p < 0.001) were significant predictors for current orofacial pain. CONCLUSIONS: PTSD was associated with self-reported awake bruxism and low-intensity orofacial pain. These conditions were frequent outcomes in patients previously exposed to traumatic events. CLINICAL RELEVANCE: We suggest including a two-question screening for bruxism in psychiatry/psychology interviews to improve under-identification and to prevent harmful consequences at the orofacial level.

A Review of the Leishmanicidal Properties of Lectins.

Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.

Purification, Characterization and Evaluation of the Anticoagulant Effect of an Uncompetitive Trypsin Inhibitor obtained from Bauhinia pulchella (Benth) Seeds.

INTRODUCTION: Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest. OBJECTIVES: This work aimed to purify a trypsin inhibitor from Bauhinia pulchella seeds (BpuTI), describing its kinetic mechanism and anticoagulant effect. METHODS: Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. In vitro assays were performed to verify its ability to prolong blood clotting time. RESULTS: Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. BpuTI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and BpuTI showed similarity to several Kunitz-type trypsin inhibitors. BpuTI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10-6 M) and Ki (1.05 x 10-6 M). Additionally, BpuTI showed high stability to temperature and pH variations, maintaining its activity up to 100ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. BpuTI showed an anticoagulant effect in vitro at a concentration of 33 µM, prolonging clotting time by 2.6 times. CONCLUSION: Our results suggest that BpuTI can be a biological tool to be used in blood clotting studies.

Cardiorespiratory coupling is associated with exercise capacity in athletes: A cross-sectional study.

PURPOSE: To determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes' subjects. METHODS: A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 - 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO2peak. RESULTS: Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = -0.1, p = 0.5) and non-athletes (r = -0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = -0.2, p = 0.3). CONCLUSION: These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).