"Unfortunately, we couldn't reach a definitive diagnosis": the interactional management of uncertainty in genetic counseling / "Infelizmente, não conseguimos chegar a um diagnóstico definitivo": a gestão interacional da incerteza no aconselhamento genético / "Lamentablemente no pudimos llegar a un diagnóstico definitivo": el manejo interaccional de la incertidumbre en el consejo genético"Lamentablemente no pudimos llegar a un diagnóstico definitivo": el manejo interaccional de la incertidumbre en el consejo genético

This paper examines how participants in genetic counseling sessions interactionally manage situations where the results of tests to investigate the causes of identified fetal malformations are inconclusive or missing. The dataset consists of 54 audio-recorded interactions at a unit specialized in moderate- and high-risk pregnancies at a Brazilian public hospital. Conversation analysis was used to examine the data, revealing that the participants deployed interactional actions that exhibited highly negative valence toward diagnostic inconclusiveness, demonstrating that when there is a motivation for a medical examination, insofar as its results will serve as a basis for subsequent decision-making (in this case about future pregnancies), there is a preference for bad diagnostic news over absent or inconclusive diagnostic news. These findings are consistent with prior interactional studies.

Este artigo examina como os participantes em sessões de aconselhamento genético gerenciam interacionalmente resultados de testes genéticos inconclusivos ou ausentes ­ testes para investigar as causas das malformações fetais identificadas. O conjunto de dados consiste em 54 interações gravadas em áudio em uma unidade de gestação de médio e alto risco de um hospital público brasileiro. A abordagem da Análise da Conversa utilizada para examinar os dados revela que os participantes desenvolvem ações interacionais que exibem uma orientação de valência altamente negativa em relação à inconclusividade diagnóstica, demonstrando que quando há motivação para um exame médico, ou seja, usando o resultado do teste diagnóstico como base para tomada de decisão, tal como acontece com futuras gestações, haja uma preferência por más notícias diagnósticas em detrimento de notícias diagnósticas ausentes ou inconclusivas. Tais resultados são consistentes com estudos interacionais anteriores.

Este artículo examina cómo los participantes en las sesiones de asesoramiento genético gestionan de forma interactiva los resultados de pruebas genéticas no concluyentes o faltantes, pruebas para investigar las causas de las malformaciones fetales identificadas. El conjunto de datos consta de 54 interacciones grabadas en audio en una unidad de embarazo de riesgo medio y alto de un hospital público brasileño. El enfoque de Análisis de Conversación utilizado para examinar los datos revela que los participantes desarrollan acciones interaccionales que exhiben una orientación de valencia altamente negativa hacia la falta de conclusión del diagnóstico, lo que demuestra que cuando hay motivación para un examen médico, es decir, utilizar el diagnóstico del resultado de la prueba como base para la toma de decisiones, como ocurre con futuros embarazos, se prefieran las malas noticias diagnósticas a las noticias diagnósticas ausentes o no concluyentes. Estos resultados son consistentes con estudios interaccionales previos.

Perspectivas multimodais sobre a comunicação com máscaras faciais em tempos de covid-19 / Multimodal perspectives on communication with face masks in times of covid-19 / Perspectivas multimodales de la comunicación con mascarillas faciales en tiempos de covid-19

Tendo em vista que nossa comunicação cotidiana mudou profundamente, estudos recentes acerca da fa-la-em-interação enfatizam a natureza holística intercorporeal que observa o paradigma intersinestésico emergente. Ao observar restrições interacionais relacionadas à nossa mobilidade limitada, ao distancia-mento social e ao uso de máscaras faciais, durante a pandemia da covid-19, elaboramos neste artigo as perguntas: o que acontece, quando o uso de máscaras faciais bloqueia partes importantes da fluência interacional e como os interactantes lidam com isso? A partir de coleta, transcrição e análise de dados em vídeos de diversos países, os seguintes resultados foram revelados: (a) levantamento da sobrancelha como marcador de acento focal; (b) ampliação do espaço gestual e utilização de gestos do tipo 'batida', quando o distanciamento social e o uso de máscaras estão em jogo; (c) a compensação da perda da expressão facial pelo uso de máscaras, por pistas entonacionais.

Recent studies on talk-in-interaction emphasize the intercorporeal holistic nature of human action. Given that our everyday communication had changed profoundly during the covid-19 pandemic, considering the interactional constraints related to our limited mobility, social distancing, and the use of face masks, we pose the following question in this article: What happens when the use of face masks blocks important parts of interactional fluency and how do interactants deal with it? Through collection, transcription, and analysis of data from videos from the first months after the outbreak, the following results were revealed: (a) raising of the eyebrow as a marker of focal accent; (b) enlargement of gestural space and frequent use of beat gestures, when social distancing and mask-wearing are at play; (c) at a micro level, compensation for the loss of facial expression due to mask-wearing, through intonational cues.

Estudios recientes sobre el habla en interacción destacan la naturaleza encarnada de la interacción. La pandemia de covid-19 ha cambiado nuestra comunicación con restricciones interactivas relacionadas con nuestra movilidad limitada, el distanciamiento social y el uso de mascarillas, por eso preguntamonos: qué ocurre cuando el uso de máscaras bloquea partes importantes de fluidez interaccional y cómo enfrentan a ello los interlocutores implicados. Hemos recopilado datos de vídeo, y mediante la recopilación, transcripción y análisis de datos de lo princípio de la pandemia, tuvimos los resultados: (a) el levantamiento de cejas pasa a primer plano como marcador de acento de tono; (b) el espacio gestual se amplía y es utilizado de forma marcada por más gestos de ritmo, cuando hay distanciamiento social y uso de mascarillas; y (c) la pérdida de expresión facial por el uso de mascarillas faciales se compensa con señales de entonación y con la ruptura del distanciamiento.

Membrane-targeted mechanism for amphiphilic vitamin C compounds as methicillin-resistant Staphylococcus aureus biofilm eradicating agents.

Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.

Ovicidal activity of diaryl dichalcogenides and ivermectin on Fasciola hepatica: A novel candidate for a blending-based therapeutic strategy.

Fasciolosis is a food and waterborne disease caused by Fasciola spp., representing a global health burden to various hosts, including humans and other animals. This study investigates the in vitro activity of tellurium- and selenium-containing diaryl dichalcogenides: diacetal ditelluride (LQ07), diacetal diselenide (LQ62), and diacetyl diselenide (LQ68) alone and in combination with ivermectin (IVM) against eggs of Fasciola hepatica. The eggs were exposed for 12 h with each organochalcogen (OC) (0.1 - 2 mmol l-1) and IVM (0.01 - 2 mmol l-1) following an incubation of 15 days, allowing embryonation. The inhibitory concentration of 50 % (IC50) of each OC or IVM was tested with the IC10, IC30, and IC50 of IVM or each OC, respectively. LQ07, LQ62, and LQ68, as well as IVM, demonstrated a concentration-dependent ovicidal activity. The peak ovicidal activity of 99.74 % was achieved when IVM was tested at 2.0 mmol l-1. LQ62 and LQ68 demonstrated greater ovicidal activity, having an IC50 < 0.32 mmol l-1 being 6.25-fold more toxic than IVM alone. The percentage of dead eggs was significantly higher in the IVM group (early mortality), as Se-containing OCs led to the (miracidia) embryonation of the eggs with no hatching (late mortality). Blending Se-containing OCs and IVM showed an additive effect of up to 27 % against F. hepatica eggs. The present data contribute to the potential use of blending-based therapeutic strategies to combat F. hepatica infections in eradication programs worldwide. The combinations may also act against multidrug-resistant strains, reinstating drug-based parasite control.

How does the life cycle of Clinodiplosis profusa (Cecidomyiidae) adjust to phenological variations of the host plant Eugenia uniflora (Myrtaceae) in sun and shade?

Galls are plant neoformations induced by specialized parasites. Since gall inducers rely on reactive plant sites for gall development, variations in abiotic factors that affect plant phenology are expected to impact the life cycle of gall inducers. To test the hypothesis that different light conditions affect both host plant and gall inducer life cycles, we studied the system Eugenia uniflora (Myrtaceae) - Clinodiplosis profusa (Cecidomyiidae), comparing plants occurring in sunny and shaded environments. We mapped phenological differences among individuals of E. uniflora occurring in the two environments and related them to the influence of luminosity on the life cycle of the gall inducer. Shade plants showed lower intensity of leaf sprouting throughout the year compared to sun-exposed plants, especially during the rainy season. Young and mature galls are synchronized with the peak of leaf sprouting at the beginning of the rainy season, lasting longer in sun-exposed plants - approximately two months longer compared to shade plants. The greater light intensity positively impacts the formation and growth of leaves and galls, with an extended period available for their induction and growth. Thus, light is an important factor for the development of gallers, considering that variations in luminosity influenced not only the phenology of the host plant, but also determined the life cycle of gall inducers. Furthermore, changes in plant-environment interactions are expected to affect the life cycle and richness of other host plant-gall inducer systems.

Deciphering the enigmatic PilY1 of Acidithiobacillus thiooxidans: An in silico analysis.

Thirty years since the first report on the PilY1 protein in bacteria, only the C-terminal domain has been crystallized; there is no study in which the N-terminal domain, let alone the complete protein, has been crystallized. In our laboratory, we are interested in characterizing the Type IV Pili (T4P) of Acidithiobacillus thiooxidans. We performed an in silico characterization of PilY1 and other pilins of the T4P of this acidophilic bacterium. In silico characterization is crucial for understanding how proteins adapt and function under extreme conditions. By analyzing the primary and secondary structures of proteins through computational methods, researchers can gain valuable insights into protein stability, key structural features, and unique amino acid compositions that contribute to resilience in harsh environments. Here, it is presented a description of the particularities of At. thiooxidans PilY1 through predictor software and homology data. Our results suggest that PilY1 from At. thiooxidans may have the same role as has been described for other PilY1 associated with T4P in neutrophilic bacteria; also, its C-terminal interacts (interface interaction) with the minor pilins PilX, PilW and PilV. The N-terminal region comprises domains such as the vWA and the MIDAS, involved in signaling, ligand-binding, and protein-protein interaction. In fact, the vWA domain has intrinsically disordered regions that enable it to maintain its structure over a wide pH range, not only at extreme acidity to which At. thiooxidans is adapted. The results obtained helped us design the correct methodology for its heterologous expression. This allowed us partially experimentally characterize it by obtaining the N-terminal domain recombinantly and evaluating its acid stability through fluorescence spectroscopy. The data suggest that it remains stable across pH changes. This work thus provides guidance for the characterization of extracellular proteins from extremophilic organisms.

The odyssey of the TR(i)P journey to the cellular membrane.

Ion channels are integral membrane proteins mediating ion flow in response to changes in their environment. Among the different types of ion channels reported to date, the super-family of TRP channels stands out since its members have been linked to many pathophysiological processes. The family comprises 6 subfamilies and 28 members in mammals, which are widely distributed throughout most tissues and organs and have an important role in several aspects of cellular physiology. It has been evidenced that abnormal expression, post-translational modifications, and channel trafficking are associated with several pathologies, such as cancer, cardiovascular disease, diabetes, and brain disorders, among others. In this review, we present an updated summary of the mechanisms involved in the subcellular trafficking of TRP channels, with a special emphasis on whether different post-translational modifications and naturally occurring mutagenesis affect both expression and trafficking. Additionally, we describe how such changes have been associated with the development and progress of diverse pathologies associated with the gain or loss of functional phenotypes. The study of these processes will not only contribute to a better understanding the role of TRP channels in the different tissues but will also present novel possible therapeutic targets in diseases where their activity is dysregulated.

Effect of Nanoscale Surface Roughness and Electron-Phonon Interaction on Vibrational Modes of Cadmium Telluride Using Resonant Raman Spectroscopy.

This study investigates the combined effects of nanoscale surface roughness and electron-phonon interaction on the vibrational modes of cadmium telluride (CdTe) using resonant Raman spectroscopy. Raman spectra simulations aided in identifying the active phonon modes and their dependence on roughness. Our results reveal that increasing surface roughness leads to an asymmetric line shape in the first-order longitudinal optical (1LO) phonon mode, attributed to an increase in the electron-phonon interaction. This asymmetry broadens the entire Raman spectrum. Conversely, the overtone (second-order longitudinal optical [2LO]) mode exhibits a symmetrical line shape that intensifies with roughness. Additionally, we identify and discuss the contributions of surface optical phonon mode and multiphonon modes to the Raman spectra, highlighting their dependence on roughness. This work offers a deeper understanding of how surface roughness and electron-phonon scattering influence the line shape of CdTe resonant Raman spectra, providing valuable insights into its vibrational properties.

Affective Implications of Human-Animal Relationship on Pig Welfare: Integrating Non-Linear Heart Rate Variability Measures.

The human-animal relationship is crucial for animal welfare. Gentle handling enhances pigs' comfort while rough handling causes fear and stress. This study examined how different human-animal relationship qualities affect the behavior and heart rate variability (linear and non-linear parameters) of 36 nursery pigs. Over six weeks, pigs experienced positive (n = 12), minimal (n = 12), or negative (n = 12) human handling. Their responses to handlers were then assessed in an experimental arena with four phases: habituation, exposure to the handler standing and sitting, and forced interaction. Pigs subjected to negative handling exhibited increased fear-related behaviors, spending less time in contact with the handler. They also exhibited heightened stress responses, with greater LF/HF ratio and Lmean values compared with positively handled pigs. Conversely, gently handled pigs displayed affiliative behaviors, accepting more strokes, and higher parasympathetic activation, indicated by greater RMSSD/SDNN and SampEn values, suggesting a more positive affective state. Minimally handled pigs exhibited some behavioral similarities to gently handled pigs, although physiological data indicated that the interaction was likely more rewarding for the gently handled pigs. These results emphasize the impact of human-animal relationships on pig welfare and highlight the value of incorporating non-linear heart rate variability parameters in such evaluations.

Proximity Sensor for Measuring Social Interaction in a School Environment.

Social interactions are characterized by being very diverse and changing over time. Understanding this diversity and dynamics, as well as their emerging patterns, is of great interest from social, health, and educational perspectives. The development of new devices has been made possible in recent years by advances in applied technology. This paper presents the design and development of a novel device composed of several sensors. Specifically, we propose a proximity sensor integrated by three devices: a Bluetooth sensor, a global positioning system (GPS) unit and an accelerometer. By means of this sensor it is possible to detect the presence of neighboring sensors in various configurations and operating conditions. Profiles based on the Received Signal Strength Indicator (RSSI) exhibit behavior consistent with that reported by empirical relationships. The present sensor is functional in detecting the proximity of other sensors and is thus useful for the identification of interactions between people in relevant contexts such as schools.

Factor analytic selection tools and environmental feature-integration enable holistic decision-making in Eucalyptus breeding.

Understanding the genotype-by-environment interaction (GEI) and considering it in the selection process is a sine qua non condition for the expansion of Brazilian eucalyptus silviculture. This study's objective is to select high-performance and stable eucalyptus clones based on a novel selection index that considers the Factor Analytic Selection Tools (FAST) and the clone's reliability. The investigation explores the nuances interplay of GEI and extends its insights by scrutinizing the relationship between latent factors and real environmental features. The analysis, conducted across seven trials in five Brazilian states involving 78 clones, employs FAST. The clonal selection was performed using an extended FAST index weighted by the clone's reliability. Further insights about GEI emerge from the integration of factor loadings with 25 environmental features through a principal component analysis. Ten clones, distinguished by high performance, stability, and reliability, have been selected across the target population of environments. The environmental features most closely associated with factor loadings, encompassing air temperature, radiation, and soil characteristics, emerge as pivotal drivers of GEI within this dataset. This study contributes insights to eucalyptus breeders, equipping them to enhance decision-making by harnessing a holistic understanding-from the genotypes under evaluation to the diverse environments anticipated in commercial plantations.

Motor Control in Parkinson's Disease During the Performance of Multi-Joint Reversal Movements.

We tested if the movement slowness of individuals with Parkinson's disease is related to their decreased ability to generate adequate net torques and linearly coordinate them between joints. This cross-sectional study included ten individuals with Parkinson's disease and ten healthy individuals. They performed planar movements with a reversal over three target distances. We calculated joint kinematics of the elbow and shoulder using spatial orientation. The muscle, interaction, and net torques were integrated into the acceleration/deceleration phases of the fingertip speed. We calculated the linear correlations of those torques between joints. Both groups modulated the elbow and shoulder net torques with target distances. They linearly coupled the production of torques. Both groups did not modulate the interaction torques. The movement slowness in Parkinson's disease was related to the difficulty in generating the appropriate muscle and net torques in the task. The interaction torques do not seem to play any role in movement control.

Influence of the agrochemical benomyl on Cryptococcus gattii-plant interaction in vitro and in vivo.

Cryptococcus gattii, an environmental fungus, is one of the agents of cryptococcosis. The influence of agrochemicals on fungal resistance to antifungals is widely discussed. However, the effects of benomyl (BEN) on fungal interaction with different hosts is still to be understood. Here we studied the influence of adaptation to BEN in the interaction with a plant model, phagocytes and with Tenebrio molitor. First, the strain C. gattii L24/01 non-adapted (NA), adapted (A) to BEN, and adapted with further culture on drug-free media (10p) interact with Nicotiana benthamiana, with a peak in the yeast burden on the 7th day post-inoculation. C. gattii L24/01 A and 10p provided lower fungal burden, but these strains increased cell diameter and capsular thickness after the interaction, together with decreased fungal growth. The strains NA and A showed reduced ergosterol levels, while 10p exhibited increased activity of laccase and urease. L24/01 A recovered from N. benthamiana was less engulfed by murine macrophages, with lower production of reactive oxygen species. This phenotype was accompanied by increased ability of this strain to grow inside macrophages. Otherwise, L24/01 A showed reduced virulence in the T. molitor larvae model. Here, we demonstrate that the exposure to BEN, and interaction with plants interfere in the morphophysiology and virulence of the C. gattii.

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.

Multi-Biomarkers' Responses in Gills of Oreochromis niloticus Exposed to Glyphosate and Polyethylene Microplastic, Isolated and in Mixture.

Microplastics (MPs) and glyphosate-based herbicides (GBH) are among the most common contaminants in aquatic environments. In Brazilian rivers, both contaminants were found in elevated levels, leading to a high probability of their association, which can alter their individual effects and potentially intensify their toxicity. This study evaluated the isolated and combined effects of polyethylene microplastics (PE-MPs) and GBH on Oreochromis niloticus using multi-biomarkers of toxicity. The fish were subjected to a 96-h exposure period, with concentrations set based either isolated, PE-MPs group (5 mg L-1), GBH group (5 mg L-1), or in a group of associated contaminants (GAC), PE-MP + GBH (5 mg L-1 + 5 mg L-1). Toxicity effects were evaluated using biochemical, cytogenetic, hematological, and histopathological biomarkers. We observed change in erythrocyte parameters leading to macrocytic normochromic anemia in GAC. Leukocyte parameters indicate a nonspecific immunosuppression caused by the exposure of associated contaminants, besides the attempts to repair damage caused by PE-MPs. Histopathological markers indicate damage to tissues exposed to contaminants. Besides, there were morphophysiological adjustments on gills, with proliferation and hypertrophy of mitochondria-rich cells on GBH and GAC, besides epithelium ruptures, which were mostly present in the exposed groups. Therefore, this study indicates that PE-MPs and GBHs present toxic effects in O. niloticus with the used concentrations, intensified by the association of contaminants. Thus, multi-biomarkers were useful key to verify toxicity, providing data to the investigation of high levels of contaminant's mixture toxicity present in aquatic environments.

Stability and genetic parameters for cassava yield attributes in the tropical humid region of Brazil.

The performance differences in cassava genotypes arising from genotype vs. environment interactions (G × E) often lead to responses that are significantly lower than expected for selection. The objective of this study was to evaluate different stability methods, both parametric and non-parametric, such as additive main-effects and multiplicative interaction (AMMI), main effect of genotypes plus G × E (GGE), and weighted average of absolute scores (WAASB), in order to quantify the G × E in multi-environmental trials. A total of 12 genotypes were assessed across 12 environments using a completely randomized block design, with three replicates for traits such as fresh root yield (FRY) and dry matter content in the roots (DMC). The data were subjected to analysis of variance and the Scott Knott test (p < 0.05). The sum of squares (SQ) of genotypes, environment, and G × E effects were equally distributed for FRY, whereas for DMC, these effects accounted for 64.1%, 21.9%, and 13.8% of the SQ, respectively, indicating a lower environmental effect on this characteristic. Using the AMMI, GGE, and WAASB methods, genotypes with high agronomic performance and stability for FRY (BR11-34-41 and BR11-34-69) (> 32 t ha-1) and DMC (BRS Novo Horizonte, BR12-107-002, and BR11-24-156) (> 37%) were identified. The broad-sense heritability ( h 2 ) for FRY and DMC was estimated to be 0.45 and 0.75, respectively. Approximately 72% of the methods identified BRS Novo Horizonte as the genotype with the highest stability and performance for DMC, while 47% identified genotypes BR11-34-41 and BR11-34-69 for FRY and intermediate DMC. Genotype BR11-24-156 exhibited high static stability according to 50% of the methods. Significant correlations were observed between stability and agronomic performance across the different methods, enabling the formation of groups based on stability concepts. Additionally, it was found that two mega-environments existed for FRY, whereas DMC displayed a single mega-environment with similar patterns, indicating an absence of G × E. We identified superior genotypes that could be promoted to national performance trials to develop stable cultivars with better yield attributes in cassava. Supplementary Information: The online version contains supplementary material available at 10.1007/s10681-024-03384-5.

Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol.

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed-dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open-label, 3-way, crossover, single-dose, prospective, and longitudinal study with a 14-day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Forty-two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time curve from 0 up to infinity (AUC0-∞) data were within the range of 80%-125%. Non-serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed-dose combination are comparable to those of the reference products.

Genotype-by-gestational thermal environment interaction and its impact on the future performance of tropical composite beef cattle offspring.

With global warming, there are growing challenges for raising taurine and composite beef cattle populations in tropical regions, including elevated temperatures, limited forage availability, parasite infestation, and infectious diseases. These environmental factors can trigger specific physiological responses in the developing fetus, which may have long-term implications on its performance. Therefore, the main objective of this study was to assess the influence of naturally induced thermal stress during the gestation period on the subsequent performance of tropical composite beef cattle progeny. Furthermore, we aimed to investigate the impact of genotype-by-gestational thermal environment interaction (G×Eg) on traits under selection pressure in the breeding population. A total of 157,414 animals from 58 farms located in various Brazilian states were recorded for birth weight (BW), preweaning weight gain (PWG), yearling weight (YW), hip height (HH), scrotal circumference (SC), and days to first calving (DFC). We first applied a linear regression model to the BW data, which revealed that the last 40 d of gestation were suitable for calculating the mean temperature humidity index (THIg). Subsequent regression analyses revealed that for every 10-unit increase in THIg, detrimental effects of approximately 1.13% to 16.34% are expected for all traits evaluated. Genetic parameters were estimated through a reaction norm model using THIg as the environmental descriptor. The posterior means of heritability estimates (SD) were 0.35 (0.07), 0.25 (0.03), 0.31 (0.03), 0.37 (0.01), 0.29 (0.07), and 0.20 (0.09) for the direct effect of BW, PWG, YW, HH, SC, and DFC, respectively. These estimates varied along the range of THIg values, suggesting a variable response to selection depending on the thermal environment during gestation. Genetic correlation estimates between more divergent THIg values were low or negative for YW, PWG, and DFC, indicating that the best-performing individuals at low THIg values may not perform as well at high THIg values and vice versa. Overall, thermal stress during gestation impacts the future performance of beef cattle offspring. Our results indicate the need for developing effective breeding strategies that take into account G×Eg effects and the re-ranking of breeding animals along the THIg scale, particularly for traits such as DFC that are highly sensitive to thermal stress.

With global warming posing increasing challenges in tropical regions, this study aimed to assess the impact of thermal stress during gestation on the performance of composite beef cattle offspring. Environmental factors such as high temperatures, humidity, limited forage availability, and parasite infestation can elicit physiological responses in the developing fetus, affecting its long-term performance and welfare. Using the temperature humidity index (THIg) of the late gestation as a measure of thermal environment, a reaction norm model was applied to analyze the birth weight, preweaning weight gain, yearling weight, hip height, scrotal circumference, and days to first calving (DFC). Results revealed that increasing THIg values were associated with a detrimental effect in these traits. Genotype-by-environment interaction was found to significantly influence trait variability, with DFC showing the strongest effect. Negative genetic correlations were observed between divergent THIg values, suggesting that individuals performing well in mild thermal environments may not excel in high thermal stress conditions. The heritability estimates varied along the THIg scale, indicating that selection response may vary depending on the thermal environment during gestation. These findings emphasize the need for breeding strategies that account for genotype-by-environment effects and consider the impact of thermal stress on cattle performance.

Antagonistic Effects of Corynebacterium pseudodiphtheriticum 090104 on Respiratory Pathogens.

In previous studies, it was demonstrated that Corynebacterium pseudodiphtheriticum 090104, isolated from the human nasopharynx, modulates respiratory immunity, improving protection against infections. Here, the antagonistic effect of the 090104 strain on respiratory pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, was explored. In a series of in vitro studies, the capacity of C. pseudodiphtheriticum 090104, its bacterium-like particles, and its culture supernatants to coaggregate, inhibit the growth, and change the virulent phenotype of pathogenic bacteria was evaluated. The results showed that the 090104 strain was able to exert a bacteriostatic effect on K. pneumoniae and S. pneumoniae growth. In addition, C. pseudodiphtheriticum 090104 coaggregated, inhibited biofilm formation, and induced phenotypic changes in all the respiratory pathogens evaluated. In conclusion, this work demonstrated that, in addition to its beneficial effects exerted by host-microbe interactions, C. pseudodiphtheriticum 090104 can enhance protection against respiratory pathogens through its microbe-microbe interactions. The mechanisms involved in such interactions should be evaluated in future research.