The immune factors involved in the rapid clearance of bacteria from the midgut of the tick Ixodes ricinus.

Ticks are obligate hematophagous arthropods that transmit a wide range of pathogens to humans as well as wild and domestic animals. They also harbor a non-pathogenic microbiota, although our previous study has shown that the diverse bacterial microbiome in the midgut of Ixodes ricinus is quantitatively poor and lacks a core. In artificial infections by capillary feeding of ticks with two model bacteria (Gram-positive Micrococcus luteus and Gram-negative Pantoea sp.), rapid clearance of these microbes from the midgut was observed, indicating the presence of active immune mechanisms in this organ. In the current study, RNA-seq analysis was performed on the midgut of I. ricinus females inoculated with either M. luteus or Pantoea sp. or with sterile water as a control. While no immune-related transcripts were upregulated by microbial inoculation compared to that of the sterile control, capillary feeding itself triggered dramatic transcriptional changes in the tick midgut. Manual curation of the transcriptome from the midgut of unfed I. ricinus females, complemented by the proteomic analysis, revealed the presence of several constitutively expressed putative antimicrobial peptides (AMPs) that are independent of microbial stimulation and are referred to here as 'guard' AMPs. These included two types of midgut-specific defensins, two different domesticated amidase effector 2 (Dae2), microplusin/ricinusin-related molecules, two lysozymes, and two gamma interferon-inducible lysosomal thiol reductases (GILTs). The in vitro antimicrobial activity assays of two synthetic mature defensins, defensin 1 and defensin 8, confirmed their specificity against Gram-positive bacteria showing exceptional potency to inhibit the growth of M. luteus at nanomolar concentrations. The antimicrobial activity of midgut defensins is likely part of a multicomponent system responsible for the rapid clearance of bacteria in the tick midgut. Further studies are needed to evaluate the role of other identified 'guard' AMPs in controlling microorganisms entering the tick midgut.

Sensory Analysis Performed within Augmented Virtuality System: Impact on Hedonic Scores, Engagement, and Presence Level.

Sensory analysis methodologies are performed in sensory booths designed to minimise external stimuli, lacking ecological validity. Immersive environments are used to introduce contextual cues, but there is a lack of studies using mixed reality systems. The main goal of this study was to evaluate an augmented virtuality (AV) system where participants are inserted into a virtual environment and evaluate a real product, being able to interact with both dimensions. A panel of 102 consumers evaluated five samples of commercial peach nectars in three sessions, each in a different environment: public food court, living room (AV environments), and laboratory (traditional sensory booth). Consumers rated overall liking, followed by open comments, and also answered an Engagement (EQ) and a Presence Questionnaire (PQ). The type of environment only affected hedonic discrimination among samples, with the laboratory setting being the only one with sample discrimination. Nonetheless, each sample was not evaluated differently across the different environments. Concerning engagement, the environment only significantly influenced the EQ's 'Affective Value' factor, being higher when using an AV system. The level of presence in the virtual environment was significantly higher in the public food court, being significantly correlated with the EQ factor scores.

Host-associated helminth diversity and microbiome composition contribute to anti-pathogen defences in tropical frogs impacted by forest fragmentation.

Habitat fragmentation can negatively impact wildlife populations by simplification of ecological interactions, but little is known about how these impacts extend to host-associated symbiotic communities. The symbiotic communities of amphibians play important roles in anti-pathogen defences, particularly against the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). In this study, we analyse the role of macroparasitic helminth communities in concert with microbial communities in defending the host against Bd infection within the context of forest fragmentation. We found that skin microbial and helminth communities are disrupted at fragmented habitats, while gut microbiomes appear more resilient to environmental change. We also detected potential protective roles of helminth diversity and anti-pathogen microbial function in limiting Bd infection. Microbial network analysis revealed strong patterns of structure in both skin and gut communities, with helminths playing central roles in these networks. We reveal consistent roles of microbial and helminth diversity in driving host-pathogen interactions and the potential implications of fragmentation on host fitness.

[A brief overview of the 2030 Agenda, noncommunicable diseases and the challenges of leaving no one behind]. / Um breve panorama sobre a Agenda 2030, as doenças crônicas não transmissíveis e os desafios de não deixar ninguém para trás.

This essay provides a theoretical reflection on the challenges of meeting the Sustainable Development Goals of the 2030 Agenda, considering its motto of "leave no one behind". To exemplify these challenges, we discuss noncommunicable diseases (NCDs), one of the main issues on the global health agenda before the COVID-19 pandemic, and the political and economic dimensions that determine their presence and global spread. After a brief overview of NCDs, the text seeks to answer three questions: In "Leaving no one behind?" we list some themes to reflect on how and who has historically been left behind, delving a little deeper into the examples in "Who has been left behind in the world?" and "Who has been left behind in Brazil?". Using data from the most relevant and recent literature on the subject, we discuss the challenges and some ways to leave no one behind in a world where the mean of production has historically made some social groups vulnerable, especially black and Indigenous populations. In our final remarks, we draw inspiration from the Sankofa ideogram to remember that the answers to the sustainable development we seek may lie somewhere in our most primordial and traditional past. And that it is necessary to invest on building new paths from different worldviews and approaches to epistemology on the other side of the abyssal line.

Este ensaio traz uma reflexão teórica sobre os desafios para alcançar as metas dos Objetivos do Desenvolvimento Sustentável da Agenda 2030, considerando seu lema de "não deixar ninguém para trás". Para exemplificar esses desafios, apresenta-se como pano de fundo as doenças crônicas não transmissíveis (DCNT), um dos principais temas da agenda da saúde global antes da pandemia de COVID-19, discutindo as dimensões políticas e econômicas que determinam sua presença e avanço global. Após um breve panorama sobre as DCNT, busca-se responder a três perguntas: em "Sem deixar ninguém para trás?", elencamos alguns temas para refletir sobre como e quem tem ficado historicamente para trás, aprofundando um pouco mais os exemplos ao adentrar em "Quem tem ficado para trás no mundo?" e "Quem tem ficado para trás no Brasil?". A partir de dados da literatura mais relevante e recente sobre o tema, apresentamos os desafios e alguns caminhos para não deixar ninguém para trás em um mundo em que o modo de produção tem historicamente vulnerabilizado alguns grupos sociais, com destaque para a população negra e a população indígena. Trazemos nas considerações finais a inspiração do ideograma Sankofa para lembrar que as respostas para o desenvolvimento sustentável que buscamos podem estar em algum lugar de nosso passado mais originário e tradicional, e que é preciso apostar na construção de novos caminhos a partir de outras epistemologias e cosmovisões presentes do outro lado da linha abissal.

Este ensayo aporta una reflexión teórica acerca de los desafíos para lograr las metas de los Objetivos de Desarrollo Sostenible de la Agenda 2030, teniendo en cuenta su lema "no dejar a nadie atrás". Para ejemplificar estos desafíos, tomamos como telón de fondo las enfermedades crónicas no transmisibles (ECNT), uno de los principales temas de la agenda de salud global antes de la pandemia de COVID-19, discutiendo las dimensiones políticas y económicas que determinan su presencia y avance global. Después de un breve panorama de las ECNT, el texto busca responder tres preguntas: En "¿Sin dejar a nadie atrás?" enumeramos algunos temas para reflexionar sobre cómo y quién ha quedado históricamente atrás, profundizando un poco más los ejemplos al centrarse en "¿Quién ha quedado atrás en el mundo?" y "¿Quién ha quedado atrás en Brasil?". Con base en datos de la literatura más relevante y reciente sobre el tema, presentamos los desafíos y algunas maneras de no dejar a nadie atrás en un mundo en el que el modo de producción ha vulnerabilizado históricamente a algunos grupos sociales, con énfasis en la población negra y en la población indígena. En nuestras consideraciones finales, nos inspiramos en el ideograma de Sankofa para recordar que las respuestas al desarrollo sostenible que buscamos pueden estar en algún lugar de nuestro pasado más original y tradicional. Y es necesario apostar por la construcción de nuevos caminos basados en otras epistemologías y cosmovisiones presentes al otro lado de la línea abisal.

Discarded substrates from soilless hydroponic horticulture as potential amendments for metal-contaminated soils.

Soil contamination with metals is a major threat for the environment and public health since most metals are toxic to humans and to non-human biota, even at low concentrations. Thus, new sustainable remediation approaches are currently needed to immobilize metals in soils to decrease their mobility and bioavailability. In this work, we explore the application of discarded substrates from hydroponic cultivation, namely coconut shell and a mixture of coconut shell and pine bark, for immobilization of metals (Cd, Cr, Ni, Cu, Pb, Hg, Sb and As) in a naturally contaminated soil from a mining region in Portugal. The immobilization capacity of substrates (added to the soil at 5% mass ratio) was assessed both individually and also combined with other traditional agriculture soil additives (limestone and gypsum, at 2% mass ratio) and nanoparticles of zero-valent iron (nZVI) at 1-3% mass ratio. The overall results obtained after a 30-d incubation showed that the discarded substrates are a viable, economic, and environmental-friendly solution for metal remediation in soils, with the capacity of immobilization ranging from 20 to 91% for the metals and metalloids studied. Furthermore, they showed the capacity to reduce the soil toxicity (EC50 ∼ 6000 mg/L) to non-toxic levels (EC50 > 10000 mg/L) to the bacteria Aliivrio fischeri.

Electroanalytical applications of ITIES - A review.

Over the last decades, the interface between two immiscible electrolyte solutions (ITIES) attracted considerable attention of the scientific community due to their vast applications, such as extraction, catalysis, partition studies and sensing. The aim of this Review is to highlight the potential of electrochemistry at the ITIES for analytical purposes, focusing on ITIES-based sensors for detection and quantification of chemically and biologically relevant (bio)molecules. We start by addressing the evolution of ITIES in terms of number of publications over the years along with an overview of their main applications (Chapter 1). Then, we provide a general historical perspective about pioneer voltammetric studies at water/oil systems (Chapter 2). After that, we discuss the most impacting improvements on ITIES sensing systems from both perspectives, set-up design (interface stabilization and miniaturization, selection of the organic solvent, etc.) and optimization of experimental conditions to improve selectivity and sensitivity (Chapter 3). In Chapter 4, we discuss the analytical applications of ITIES for electrochemical sensing of several types of analytes, including drugs, pesticides, proteins, among others. Finally, we highlight the present achievements of ITIES as analytical tool and provide future challenges and perspectives for this technology (Chapter 5).

Cross-cultural adaptation and validation of the CFAbd-Score for gastrointestinal symptoms in patients with cystic fibrosis.

OBJECTIVE: Translating and cross-culturally adapting the CFAbd-Score, Cystic Fibrosis (CF) Abdominal Score, to use in Brazilian spoken Portuguese. The CFAbd-Score is a questionnaire for assessing CF-related abdominal symptoms and their influence on the quality of life (QoL). It comprises 28 questions on five domains: abdominal pain, bowel movements, eating and appetite, gastroesophageal reflux symptoms, and the impact of gastrointestinal (GI) symptoms on QoL. METHOD: Cross-cultural adaptation included assessment of conceptual and item equivalence, semantic, operational, and measurement equivalence. Content validity was assessed. The validation and psychometric analysis phase included 97 people with CF (pwCF), median age:14.58y (IQR 9/19), and 105 healthy individuals, 15.10y (IQR 9/20). Exploratory factor analysis (FA) identified retained factors. Internal consistency of the extracted domains was evaluated using Cronbach's α, and the Kaiser-Meyer-Olkin test (KMO) was used to check the sample adequacy. Bartlett's test tested the null hypothesis that the correlation matrix is an identity matrix. RESULTS: All items were considered relevant to the construct and good semantic equivalence of the version was recognized. FA showed the appropriate weight of all items and good internal consistency, with Cronbach's alpha 0.89. Bartlett's test significance level (p < 0.001) and KMO coefficient of 0.72 indicated good adequacy for structure. Internal consistency coefficients (Cronbach's alpha) were good for abdominal pain: 0.84; abdominal bloating: 0.73; flatulence: 0.76; heartburn: 0.81, and low for reflux: 0.54. CONCLUSION: The CFAbd-Score was adapted to the Brazilian spoken Portuguese and demonstrated content and semantic equivalence. The final version showed appropriate validity, and internal consistency, preserving the psychometric properties of the original version.

Pre-harvest application of sodium nitroprusside enhances storage root quality in red beet cultivated under normal and drought conditions.

BACKGROUND: The role of nitric oxide (NO) in plant stress tolerance, as well as in increasing post-harvest quality, has been extensively demonstrated in several fruits and vegetable crops; however, the effects of its pre-harvest application on post-harvest quality are still poorly documented. Therefore, the pre-harvest application of NO in red beet (Beta vulgaris subsp. vulgaris) plants cultivated under well-watered and drought conditions was evaluated to assess whether it improves the post-harvest quality of their storage roots. Red beet plants cultivated under well-watered (80% of water holding capacity) or drought condition (15% of water holding capacity) were sprayed weekly with water (control) or 100 µmol L-1 sodium nitroprusside (SNP), an NO donor. Sixty-six days after sowing, red beet roots were harvested, and root yield, total sugar yield, reducing sugars, non-reducing sugars, proteins, lipids, root ashes, root moisture, soluble solids, titratable acidity, pH, vitamin C, total phenolics, total betalains, betacyanins, betaxanthins and antioxidant capacity were determined. RESULTS: While drought led to a reduction in root yield, sugars, lipids and titratable acidity, it increased phenolic compounds, betalains and the antioxidant capacity of beets. SNP reversed the negative effects of drought on sugar, lipid and organic acid contents and increased antioxidant capacity independent of stress. CONCLUSION: Pre-harvest SNP treatment reversed drought-induced yield reductions in beets, while boosting bioactive compounds and antioxidant capacity. It also enhanced vitamin C content independently, indicating its dual role in stress mitigation and beet quality improvement. Future research should explore other crops and stress conditions. © 2024 Society of Chemical Industry.

Synthesis of Silver Nanoparticles Using Extracts from Different Parts of the Paullinia cupana Kunth Plant: Characterization and In Vitro Antimicrobial Activity.

The green synthesis of silver nanoparticles (AgNPs) can be developed using safe and environmentally friendly routes, can replace potentially toxic chemical methods, and can increase the scale of production. This study aimed to synthesize AgNPs from aqueous extracts of guarana (Paullinia cupana) leaves and flowers, collected in different seasons of the year, as a source of active biomolecules capable of reducing silver ions (Ag+) and promoting the stabilization of colloidal silver (Ag0). The plant aqueous extracts were characterized regarding their metabolic composition by liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS/MS), phenolic compound content, and antioxidant potential against free radicals. The synthesized AgNPs were characterized by UV/Vis spectrophotometry, dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and scanning electron microscopy coupled to energy-dispersive X-ray spectrometry (EDX). The results demonstrated that the chemical characterization indicated the presence of secondary metabolites of many classes of compounds in the studied aqueous extracts studied, but alkaloids and flavonoids were predominant, which are widely recognized for their antioxidant capabilities. It was possible to notice subtle changes in the properties of the nanostructures depending on parameters such as seasonality and the part of the plant used, with the AgNPs showing surface plasmon resonance bands between 410 and 420 nm using the leaf extract and between 440 and 460 nm when prepared using the flower extract. Overall, the average hydrodynamic diameters of the AgNPs were similar among the samples (61.98 to 101.6 nm). Polydispersity index remained in the range of 0.2 to 0.4, indicating that colloidal stability did not change with storage time. Zeta potential was above -30 mV after one month of analysis, which is adequate for biological applications. TEM images showed AgNPs with diameters between 40.72 to 48.85 nm and particles of different morphologies. EDX indicated silver content by weight between 24.06 and 28.81%. The synthesized AgNPs exhibited antimicrobial efficacy against various pathogenic microorganisms of clinical and environmental interest, with MIC values between 2.12 and 21.25 µg/mL, which is close to those described for MBC values. Therefore, our results revealed the potential use of a native species of plant from Brazilian biodiversity combined with nanotechnology to produce antimicrobial agents.

Ten years of directing seeding restoration in the Brazilian savanna: Lessons learned and the way forward.

Savannas and grasslands have lost almost 50% of their original cover worldwide. Therefore, the development of methods and information on open-canopy ecosystem restoration is urgent for the inclusion of these ecosystems into global and regional priorities. In the Brazilian savanna, the most diverse savanna in the world, restoration efforts focused on open ecosystems have been virtually absent, but have increased in the last 10 years. Such efforts are frequently threatened by invasive exotic grasses (IEG) that invade and dominate areas excluding native species, oftentimes aided by altered soil conditions. Long-term studies of savanna restoration trajectories are rare. In this study, we surveyed 22 savanna restoration areas established two to ten years before the study with similar restoration methods to assess their current status. We show that the current restoration methods are successful in establishing native species and allowing species turnover but they are threatened by IEG. Restoration success varies and is affected by soil conditions, IEG landscape cover and post-sowing weeding. Despite that, the simultaneous introduction of different plant functional groups allows turnover from fast to slow-growing plants. Establishing savanna native species is possible at an operational scale with current knowledge and techniques. However, native species establishment fails to prevent IEG reinfestation, which needs to be managed in restoration efforts in the Brazilian savanna.

Insights into Aspergillus fumigatus Colonization in Cystic Fibrosis and Cross-Transmission between Patients and Hospital Environments.

BACKGROUND: Approximately 60% of individuals with cystic fibrosis (CF) are affected by Aspergillus fumigatus infection. This condition is correlated with a decline in lung function and is identified as an independent risk factor contributing to hospital admissions among CF patients. This study investigates the dynamic interplay of A. fumigatus within the context of CF patients, tracing its evolution over time, with a specific emphasis on colonization dynamics. METHODS: An analysis was conducted on 83 sequential A. fumigatus isolates derived from sputum samples of six patients receiving care at a renowned CF hospital in Brazil. Employing microsatellite genotyping techniques, alongside an investigation into cyp51A gene mutations, this research sheds light on the genetic variations, colonization, and resistance of A. fumigatus within the CF respiratory environment. RESULTS: Our research findings indicate that CF patients can harbor A. fumigatus strains from the same clonal complexes for prolonged periods. Additionally, we identified that clinical isolates have the potential to spread among patients in the same healthcare facility, evidencing hospital contamination. Two patients who underwent long-term Itraconazole treatment did not show phenotypic resistance. However, one of these patients exhibited mutations in the cyp51A gene, indicating the need to monitor resistance to azoles in these patients colonized for long periods by A. fumigatus. We also observed co-colonization or co-infection involving multiple genotypes in all patients over time. CONCLUSION: This comprehensive examination offers valuable insights into the pathogenesis of A. fumigatus infections in CF patients, potentially shaping future therapeutic strategies and management approaches. This enhanced understanding contributes to our knowledge of A. fumigatus impact on disease progression in individuals with cystic fibrosis. Additionally, the study provides evidence of cross-contamination among patients undergoing treatment at the same hospital.

Exploring the midgut physiology of the non-haematophagous mosquito Toxorhynchites theobaldi.

Toxorhynchites mosquitoes have an exclusively phytophagous feeding habit as adults, which leads to significant differences in their morphophysiology compared with haematophagous mosquitoes. However, the molecular mechanisms of digestion in this mosquito are not well understood. In this study, RNA sequencing of the posterior midgut (PMG) of the mosquito Toxorhynchites theobaldi was undertaken, highlighting its significance in mosquito digestion. Subsequently, a comparison was made between the differential gene expression of the PMG and that of the anterior midgut. It was found that the most abundant proteases in the PMG were trypsin and chymotrypsin, and the level of gene expression for enzymes essential for digestion (such as serine protease, α-amylase and pancreatic triacylglycerol lipase) and innate immune response (including catalase, cecropin-A2 and superoxide dismutase) was like that of haematophagous mosquitoes. Peritrophin-1 was detected in the entire midgut, with an elevated expression level in the PMG. Based on our findings, it is hypothesized that a non-haematophagic habit might have been exhibited by the ancestor of Tx. theobaldi, and this trait may have been retained. This study represents a pioneering investigation at the molecular level of midgut contents in a non-haematophagous mosquito. The findings offer valuable insights into the evolutionary aspects of feeding habits in culicids.

Gamma-rays and X-rays spectrometries applied to evaluate soil redistribution.

This work responds to the growing global demand for food, which requires improvements in agricultural production and sustainable management of natural resources. The focus is on soil erosion as a critical element in preserving agricultural productivity. From this perspective, the levels of radionuclides and chemical elements present in the soil, quantified through Gamma-Rays Spectrometry (GRS) and Energy Dispersive X-ray Fluorescence (EDXRF), were used to investigate soil redistribution over time. 27 soil samples ranging from 0 to 30 cm in depth were collected in an agricultural plot located in southern Brazil. Quantitative analysis indicated high mean concentrations of Fe (161 ± 7 gkg-1), Al (110 ± 17 gkg-1), Ca (2.6 ± 0.5 gkg-1), Mn (2.4 ± 0.3 gkg-1) and K (543 ± 165 mgkg-1) in comparison with the other detected elements. The quantification of 137Cs provided a mean inventory of 27 ± 17 Bqm-2. Using the proportional model, an estimated gross erosion rate of 28.2 tonha-1year-1 and a net soil deposition of 6.6 tonha-1year-1 were calculated. Therefore, a net soil loss of 21.6 tonha-1year-1 was experienced within the agricultural plot studied. The data set combination of both techniques with Principal Component Analysis (PCA) revealed correlations between the variables studied and the soil erosion dynamics. The PCA showed a tendency to separate the samples according to their sampling depth. Moreover, 137Cs behavior in soil proved to be similar to the behavior of elements found in fertilizers, like K. On the other hand, the individual influence of 137Cs was not enough to cause significant changes in the samples distribution in the scores plot, highlighting EDXRF as a promising technique to complement soil erosion studies.

Impact of right ventricle-pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation.

Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI.  Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed.  Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality.  V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care.

Systematic Review of Emotion Detection with Computer Vision and Deep Learning.

Emotion recognition has become increasingly important in the field of Deep Learning (DL) and computer vision due to its broad applicability by using human-computer interaction (HCI) in areas such as psychology, healthcare, and entertainment. In this paper, we conduct a systematic review of facial and pose emotion recognition using DL and computer vision, analyzing and evaluating 77 papers from different sources under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our review covers several topics, including the scope and purpose of the studies, the methods employed, and the used datasets. The scope of this work is to conduct a systematic review of facial and pose emotion recognition using DL methods and computer vision. The studies were categorized based on a proposed taxonomy that describes the type of expressions used for emotion detection, the testing environment, the currently relevant DL methods, and the datasets used. The taxonomy of methods in our review includes Convolutional Neural Network (CNN), Faster Region-based Convolutional Neural Network (R-CNN), Vision Transformer (ViT), and "Other NNs", which are the most commonly used models in the analyzed studies, indicating their trendiness in the field. Hybrid and augmented models are not explicitly categorized within this taxonomy, but they are still important to the field. This review offers an understanding of state-of-the-art computer vision algorithms and datasets for emotion recognition through facial expressions and body poses, allowing researchers to understand its fundamental components and trends.

Development and validation of a stability-indicating method, structural elucidation of new degradation products from misoprostol by LC-MS time-of-flight, and an ex vivo study of vaginal permeation.

Misoprostol (MSP) is commonly prescribed in obstetrics and gynecology clinical practice for labor induction, cervical ripening, first-trimester pregnancy termination, and the treatment of postpartum hemorrhage. Furthermore, there is a lack of comprehensive discussion evaluating how different commercially available formulations influence the overall efficacy of MSP, even though reports indicate issues with the quality of these formulations, particularly regarding stability and vaginal absorption processes. This study investigates the stability of MSP under acidic conditions and its in vitro permeation using swine vaginal mucosa. A forced degradation study was conducted using 0.2 M HCl, and a high-efficiency LC method was developed. Three degradation products were identified and characterized using electrospray ionization-high-resolution quadrupole-time-of-flight-MS, with respective m/z values of 391.2508, 405.2705, and 387.2259, respectively. These results suggest that the degradation mechanism involves dehydration of the ß-hydroxy ketone moiety, followed by isomerization to its most resonance-stable form and de-esterification. Finally, the in vitro permeation study revealed that the esterified form of MSP was unable to permeate the mucosa and required prior degradation for any component to be detected in the receptor fluid.

Bronchodilator response assessment through impulse oscillometry system and spirometry in children and adolescents with cystic fibrosis.

OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.

Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM.

Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly.