Search

Chagas disease is caused by the parasite Trypanosoma cruzi. It is a common cause of heart disease in endemic areas of Latin America. The year 2009 marks the 100th anniversary of the discovery of T cruzi infection and Chagas disease by the Brazilian physician Carlos Chagas. Chagasic cardiomyopathy develops in from 10% to 30% of persons who are chronically infected with this parasite. Echocardiography and magnetic resonance imaging (MRI) are important modalities in the evaluation and prognostication of individuals with chagasic heart disease. The etiology of chagasic heart disease likely is multifactorial. Parasite persistence, autoimmunity, and microvascular abnormalities have been studied extensively as possible pathogenic mechanisms. Experimental studies suggest that alterations in cardiac gap junctions may be etiologic in the pathogenesis of conduction abnormalities. The diagnosis of chronic Chagas disease is made by serology. The treatment of this infection has shortcomings that need to be addressed. Cardiac transplantation and bone marrow stem cell therapy for persons with Chagas disease have received increasing research attention in recent years. [ABSTRACT FROM AUTHOR]

AIMS: With the purpose of studying left ventricular filling in Chagas' disease (Chd), we evaluated 169 patients with Chd using echocardiography and Doppler and tissue Doppler imaging (TDI). METHODS AND RESULTS: The patients were divided into four groups according to the pattern of left ventricular filling: Group 0--normal filling pattern, Group 1--abnormal relaxation, Group 2--pseudonormal flow pattern, and Group 3--restrictive pattern. All patients were submitted to TDI of the basal portion of the left ventricle's walls. Diastolic dysfunction was found in 21.3% of the patients, with a strong correlation between the worsening of diastolic function and ejection fraction (r = 0.78, P < 0.001). TDI septal e' wave measurement was the best method for the detection of any kind of diastolic dysfunction. Considering a cut-off point of 11 cm/s, a reduced e' wave value has 97% sensitivity, 84% specificity, 62% positive predictive value, and 99% negative predictive value. The septal E/e' ratio was the best index for the detection of advanced diastolic dysfunction. Considering a cut-point of 7.2, an elevated E/e' ratio has 100% sensitivity, 88% specificity, 54.2% positive predictive value, and 100% negative predictive value. CONCLUSION: This study showed the characterization of the various patterns of left ventricle diastolic function by echocardiography and Doppler in Chagas' disease and the usefulness of TDI in the assessment of diagnosis of diastolic dysfunction in this disease. [ABSTRACT FROM AUTHOR]

Heart rate turbulence (HRT) quantifies the biphasic response of the sinus node to ventricular premature complexes (VPCs) and is a powerful electrocardiogram related risk predictor. VPCs are frequent in Chagas disease, a potentially lethal illness, and can hamper the analysis by conventional methods of autonomic heart control. The aim of the study was to examine HRT in patients with Chagas disease. Chagas disease patients and healthy controls (group 0, n = 11) without other diseases were submitted to a standardized protocol, including electrocardiogram, echocardiography, and 24-hour Holter monitoring. Chagas disease patients were divided according to their left ventricular systolic function: normal (group 1, n = 103) and reduced ejection fraction (group 2, n = 23). Two HRT indices, turbulence onset (TO) and turbulence slope (TS), were calculated and compared among groups after adjustment for covariates like the prevalence of VPCs and the mean heart rate. Chagas disease patients had significantly altered TO (group 1: -0.0186, group 2: -0.0126) and TS (group 1: 10.844, group 2: 7.870) values in comparison with controls (TO -0.0256, TS 19.829); P < 0.001 for both comparisons. In conclusion, HRT data may be useful in the electrocardiographic analysis of autonomic heart control in Chagas disease. Its prognostic value remains to be determined. [ABSTRACT FROM AUTHOR]

Chronic Chagas cardiomyopathy is associated with an unbalanced immune response and impaired heart function, and available drugs do not prevent its development. Zileuton (Zi), a 5-lypoxigenase inhibitor, affects inflammatory/pro-resolution mediators. Herein, Zi treatment in the early phase of infection reduced parasitemia associated mainly with the direct effect of Zi on the parasite, and the enzyme epoxide hydrolase was the potential molecular target behind the trypanocidal effect. In the intermediate acute phase of infection, Zi reduced the number of innate and adaptive inflammatory cells, increased the level of SOCS2 expression in the heart associated with lower inflammation, and improved cardiac function. Zi treatment initiated in the chronic stage increased the level of SOCS2 expression in the heart, reduced inflammation, and improved cardiac function. Our data suggest that Zi protects against Trypanosoma cruzi infection by acting directly on the parasite and reducing heart damage and is a promising option for the treatment of Chagas disease.

Rationale: Elevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen-presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood., Objective: We aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin-induced pulmonary fibrosis in mice., Methods: We used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c-DTR-Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin-induced lung inflammation and fibrosis., Results: Fourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c-DTR-Tg mice protected against bleomycin-induced mortality and pulmonary fibrosis compared to wild-type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis-related mRNAs (Collagen-1α1 and α-SMA). Increased anti-inflammatory cytokine IL-10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL-1β, with lung hyper-inflammation and early fibrosis development., Conclusion: Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

30 Nellore animals with an average weight of 407.25 ± 2.04 kg, were distributed in a completely randomized design across the following treatments: 1-Control (without inclusion of 3-NOP); 2-BV75 (inclusion of 3-NOP at 75 mg/kg DM); 3-BV100 (inclusion of 3-NOP at 100 mg/kg DM). No significant effects were observed between treatments on ingestive behavior. However, the notable effect on the BWfinal and ADG of animals supplemented with 3-NOP compared to the control group was measurable. Cattle beef receiving 3-NOP exhibited reduced methane emissions ( p < 0.0001) for all variables analyzed, resulting in an average decrease of 38.2% in methane emissions compared to the control, along with increased hydrogen emissions (g/day) ( p < 0.0001). While supplementation with BV100 demonstrated lower methane emission, the performance was lower than BV75 in DMI, BWfinal, ADG, and ADG carcasses. Partial separation of metabolomics observed between groups indicated changes in meat metabolism when comparing the control group with the 3-NOP group, identifying metabolites with a variable importance projection (VIP) score > 1. In conclusion, supplementation with 3-NOP effectively reduced methane emissions and did not negatively influence animal performance.

This study aimed to assess the effect of bulk tank milk (BTM), waste milk (WM), and pasteurized waste milk (PWM) on nutrient digestibility, ruminal and cecal fermentation, gastrointestinal tract (GIT) development, and antimicrobial resistance of fecal Escherichia coli from dairy calves at 2 periods (30 and 60 d of age). Calves were grouped according to BW, serum protein levels, and breed composition. Three treatments were included: BTM (n = 21), WM from cows under antibiotic treatment (n = 21), and PWM (WM submitted to HTST pasteurization; n = 21). A total of 63 calves were used, of which 18 animals (n = 6 per treatment) were evaluated in the period of 4 to 30 d, and 45 (n = 15 per treatment) from 4 to 60 d. During the experimental period, a daily intake of 6 L of milk was divided into 2 equal meals, with ad libitum access to water and starter. Milk and feed intakes were recorded daily. Apparent total-tract digestibility and nitrogen balance were conducted from 25 to 29 d of age (n = 6) and from 53 to 57 d of age (n = 15). Animals were slaughtered at 30 ± 1 and 60 ± 1 d of age for the assessment of ruminal and cecal fermentation and GIT development. Antimicrobial susceptibility testing was conducted at 1, 30, and 60 d of age (n = 15/treatment). Statistical analysis used a linear mixed-effects model for continuous outcomes and generalized linear models for single measurements (R software). Treatments WM and PWM had lower rumen pH, higher ruminal acetate concentration, larger reticulorumen and liver, and a higher prevalence of fecal-resistant E. coli compared with BTM at both 30 and 60 d. Up to 60 d, both BTM and WM treatments exhibited higher digestibility of ether extract and gross energy compared with the PWM, whereas WM and PWM treatments showed increased nitrogen intake and retention compared with the BTM treatment. These findings suggest that pasteurization of WM negatively affects nutrient digestibility and calf performance, while also affecting rumen development. Additionally, the use of milk containing antibiotic residue leads to the selection of resistant E. coli in the GIT over time., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Our objective was to estimate the requirements of metabolizable energy (ME) and NE M of lactating and dry cows, the efficiency of ME utilization for milk production (k l ) and tissue gain (k g ), and the use of body energy mobilization for milk production (k t ) throughout the lactation of primiparous crossbred Holstein × Gyr cows, using open-circuit respiration chambers. Twenty-nine primiparous Holstein × Gyr crossbred cows with an initial BW averaging 563 ± 40.1 kg and 2.5 ± 0.09 yr old were used throughout lactation and dry periods. The cows were kept nonpregnant throughout the study to eliminate possible confounding factors. Apparent digestibility assays, followed by calorimeter measurements, were performed 6 times throughout the lactation period. In the dry-off period, the cows were also evaluated but fed with restricted intake (DMI = 1.1% BW/d) to achieve heat production close to maintenance. After 21 d of diet adaptation, an apparent digestibility assay followed by calorimeter measurements was performed. Parameter estimates for lactation period were obtained by mixed models including lactation stage as repeated measures. For restricted feeding at dry-off and fasting period assays, the requirements were estimated by exponential regression. For whole lactation, the values of the ME requirement for maintenance (ME M ) and NE M were 0.588 and 0.395 MJ/BW 0.75 , respectively. The efficiencies of k l , k g , and k t were 0.672, 0.771, and 0.814, respectively. However, ME M and NE M were higher in early and mid lactation than late, whereas k l was higher in early than other lactation stages. Dry and nonpregnant cows had ME M of 0.434 MJ/BW 0.75 and NE M of 0.351 MJ/BW 0.75 for maintenance level, and ME M of 0.396 MJ/BW 0.75 and NE M of 0.345 MJ/BW 0.75 for fasting metabolism level, and efficiency of ME utilization for maintenance was 0.80. Our findings confirmed that F 1 crossbred Holstein × Gyr dairy cows have differences in energy requirement and efficiency throughout the lactation stages, suggesting the use of different values in each stage. The estimated values of energy requirement for maintenance and efficiencies for primiparous lactating crossbred Holstein × Gyr were similar to those reported in the literature in specific studies and requirements systems., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach's myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development.

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species. Here we present a data set from camera trap surveys of medium to large-sized native mammals (>1 kg) across the Atlantic Forest. We compiled data from 5380 ground-level camera trap deployments in 3046 locations, from 2004 to 2020, resulting in 43,068 records of 58 species. These data add to existing data sets of mammals in the Atlantic Forest by including dates of camera operation needed for analyses dealing with imperfect detection. We also included, when available, information on important predictors of detection, namely the camera brand and model, use of bait, and obstruction of camera viewshed that can be measured from example pictures at each camera location. Besides its application in studies on the patterns and mechanisms behind occupancy, relative abundance, richness, and detection, the data set presented here can be used to study species' daily activity patterns, activity levels, and spatiotemporal interactions between species. Moreover, data can be used combined with other data sources in the multiple and expanding uses of integrated population modeling. An R script is available to view summaries of the data set. We expect that this data set will be used to advance the knowledge of mammal assemblages and to inform evidence-based solutions for the conservation of the Atlantic Forest. The data are not copyright restricted; please cite this paper when using the data., (© 2024 The Ecological Society of America.)

We aimed to evaluate the effects of different drying methods for banana residues on the energy metabolism and respirometry of growing lambs. Twenty Santa Inês x Dorper lambs were fed five experimental diets: Tifton 85 grass hay (Control), shade-dried banana leaf hay (LH Shade), shade-dried pseudostem banana hay (PH Shade), sun-dried banana leaf hay (LH Sun), and sun-dried banana pseudostem hay (PH Sun). Nutrient intake and digestibility were assessed in metabolic cages, whereas O 2 consumption and CO 2 , methane, and heat production were measured in a respirometry chamber with animals fed at maintenance and ad libitum levels. Nutrient and energy intake was not influenced by diet. Pseudostem hay had higher apparent digestibility of dry matter (71.5%), organic matter (72.4%), and neutral detergent fiber (58.0%). However, this led to greater energy loss in the form of methane (12.1%). The banana residue hays and drying methods did not alter oxygen consumption, CO 2 production, or heat production of animals fed ad libitum or during maintenance. On the other hand, the use of leaf hay resulted in a reduction of 24.7% in enteric methane production of animals fed ad libitum. The inclusion of pseudostem hay is recommended in sheep feedlot diet. This residue provided greater use of DM, however promoted a greater loss of energy in the form of methane, resulting in similar energy consumption. The drying methods did not reduce the availability of nutrients and the sun drying method is recommended, since it is a faster drying method., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The aim of the study was to evaluate the effect of total mixed ration particle size (length) and breed of cow on intake dynamics, animal performance and CH 4 emissions, comparing high yielding Holstein and low yielding Girolando cows. The experimental design was 2 × 2 Latin Square arranged as a crossover factorial scheme with two diets (short particle size, SPS and long particle size, LPS) and the two breed compositions. The design comprised two periods of 26 d each, where all data collection was performed at cow level. No influence of the particle size occurred for the passage rate, neutral detergent fiber digestibility, performance and milk composition, methane emissions or ruminal fermentation parameters. Girolando cows had greater dry matter intake (DMI) when fed SPS, while Holsteins had the same ( P < 0.05). Girolando cows had lower dry matter digestibility when fed LPS compared to SPS, while Holsteins had the opposite effect ( P < 0.05). Also, the digestibility of crude protein and non-fibrous carbohydrates decreased in Girolando cows fed LPS, but not in Holsteins ( P < 0.05). Girolando cows reduced DMI by 10.6% when fed LPS diet ( P < 0.05). Girolando had an increased eating rate (+24 g of DM/min; P < 0.05) compared to Holstein cows, but Holstein cows had a lower CH 4 intensity (by 29.7%: P < 0.05). Girolando cows increased the dry matter intake when fed a diet with short particle size, while the same did not happen in Holsteins. Dry matter digestibility increased in Holsteins when fed long particle size, while the opposite was observed in Girolando cows. Nutrient digestibility was reduced in Girolando cows when fed short particle size. Particle size did not influence eating time, eating rate, feed trough visits, visits with intake, milk yield and composition regardless of the breed. Reducing particle size increased CH 4 intensity in both breeds.

Diarrhea and respiratory diseases pose significant challenges in the rearing of pre-weaned calves, motivating the investigation of tools to improve gastrointestinal tract development, health, and overall performance in young calves. Consequently, the primary objective of this study was to assess the effectiveness of an additive incorporated into milk replacer to promote the development and health of the animals. Forty-six dairy calves were randomly assigned into two treatments: control (CON, n = 23; with 15 females and 8 males), and sodium butyrate (SB, n = 23; with 15 females and 8 males). The calves in the SB treatment group were supplemented with 4 g/d of unprotected sodium butyrate (Adimix, Adisseo, China), added to the milk replacer from 4 to 60 days of age. Water and starter were fed ad libitum. The study evaluated several parameters, including feed intake, nutrient digestibility, ruminal pH, ammonia and volatile fatty acids, blood metabolites (glucose, insulin-like growth factor type 1, urea, β-hydroxybutyrate), hemogram, health scores, performance, and feed efficiency. Bull calves were euthanized at 60 days of age for organ comparison, while heifer calves were assessed for carryover effects up to 90 days of age. Data were analyzed independently using linear mixed models using the nlme package in R, and the Artools package for non-parametric categorical outcomes. Although the feed intake and performance variables exhibited differences within weeks, no divergence was observed between treatment groups. Notably, a positive treatment-by-week interaction was identified for starter feed intake ( p = 0.02) and total dry matter intake ( p = 0.04) during pre-weaning for CON animals. Ruminal parameters, blood metabolites, and hemogram values such as glucose, urea, insulin-like growth factor type 1, mean corpuscular value, lymphocytes, and neutrophils displayed differences within weeks during the pre-weaning stage, but similar results within groups. No differences between supplemented and non-supplemented calves were found across nutrient digestibility, organ development, and histology. Regarding health scores, differences were noted within weeks for fecal and respiratory scores during the pre-weaning stage, and only the respiratory score during the post-weaning stage. Consequently, butyrate supplementation did not elicit improvements or negative effects in the body development or health status of dairy calves.

In this work, two analogous coumarin-thio and semicarbazone hybrid compounds were prepared and evaluated as a potential antichagasic agents. Furthermore, palladium and platinum complexes with the thiosemicarbazone derivative as ligand (L1) were obtained in order to establish the effect of metal complexation on the antiparasitic activity. All compounds were fully characterized both in solution and in solid state including the resolution of the crystal structure of the palladium complex by X-ray diffraction methods. Unexpectedly, all experimental and theoretical characterizations in the solid state, demonstrated that the obtained palladium and platinum complexes are structurally different: [PdCl(L1)] and [PtCl 2 (HL1)]. All the studied compounds lower the proliferation of the amastigote form of Trypanosoma cruzi while some of them also have an effect on the trypomastigote stage. Additionally, the compounds inhibit T. cruzi release from host cells in variable extents. The Pd compound presented a remarkable profile in all the in vitro experiments, and it showed no toxicity for mammalian cells in the assayed concentrations. In this sense, in vivo experiments were performed for this compound using an acute model of Chagas disease. Results showed that the complex significantly lowered the parasite count in the mice blood with no significant toxicity., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

We aimed to estimate the protein requirements of pregnant Holstein × Gyr cows. A total of 61 Holstein × Gyr (HG) cows were used, with an average initial body weight (BW) of 480 ± 10.1 kg and age 5 ± 0.5 yr. Cows were divided into 3 groups: pregnant (n = 43), nonpregnant (n = 12), and baseline (n = 6). Baseline animals were slaughtered before starting the experiment to estimate the initial body composition of the remaining animals. Pregnant and nonpregnant cows received 2 diets: maintenance and ad libitum. Pregnant cows were slaughtered at 139, 199, 241, and 268 gestation days (GD). First, we used data only from nonpregnant cows to determine the requirements for maintenance and growth in adult cows. The requirements of metabolizable protein for maintenance (MP m ; grams of empty metabolic BW [EBW 0.75 ] per day) were estimated using a linear regression between the metabolizable protein intake (MPI, g/d) and average daily gain (g/d), and the MP m was defined as the intercept divided by the average metabolic BW. Net protein requirements for gain (NP g ; g/d) were estimated by the first derivative of the allometric equation between final crude protein in the body (kg) and the final empty BW (EBW; kg). The efficiency of use of metabolizable protein for gain (k) was calculated from the regression between the retained protein (g EBW 0.75 /d) and the MPI (g EBW 0.75 /d), and k was the slope of this regression. The MPI was estimated by combining microbial protein synthesis (purine derivatives) with the digestible rumen undegradable protein [(total protein intake - rumen-degradable protein) × intestinal digestibility]. Second, an exponential model was used to fit the protein accumulation in the gestational components in the function of GD. The first derivative of that model was considered the net requirement for gestation (NP gest ). The efficiency of protein utilization for gestation (k gest ) was calculated by the iterative method using the equation Δ = MPI - (MP m + NP g /k g + NP gest /k gest ), where k g is efficiency of protein utilization for gain. The iteration was performed aiming at a zero deviation between observed MPI and metabolizable protein (MP) estimated by the requirements determined herein. We obtained a value of 3.88 g EBW 0.75 /d for MP m . The estimation of NP g can be calculated according to the following equation: NP g = 0.716 × (EBW open -0.308 ) × EBG c , where EBW open is the EBW (kg) for nonpregnant animals and EBG c is the empty body gain (kg/d) corrected for the gestational component. The k was determined as 0.347. The NP gest requirements were determined as NP gest (g/d) = 0.0008722 × exp (0.01784 × GD) × (calf weight/35). The k gest was 0.625. It is important to highlight that different methods of MP estimates should not be mixed and that the proposed method requires the estimation of microbial protein (estimated via urinary estimates), which might limit practical application. In conclusion, new studies should be conducted to validate our results and the methodology adopted to determine protein requirements for pregnancy in dairy cows. Due to the pattern of protein accumulation in the gestational components, we suggest an exponential model to describe protein requirements for pregnancy for dairy cows., (© 2024, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4 + -, and Treg CD8 + -producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host's capacity to deal with infection.

Over 110 years after the first formal description of Chagas disease, the trypanocidal drugs thus far available have limited efficacy and several side effects. This encourages the search for novel treatments that inhibit T. cruzi targets. One of the most studied anti-T. cruzi targets is the cysteine protease cruzain; it is associated with metacyclogenesis, replication, and invasion of the host cells. We used computational techniques to identify novel molecular scaffolds that act as cruzain inhibitors. First, with a docking-based virtual screening, we identified compound 8, a competitive cruzain inhibitor with a K i of 4.6 μM. Then, aided by molecular dynamics simulations, cheminformatics, and docking, we identified the analog compound 22 with a K i of 27 μM. Surprisingly, despite sharing the same isoquinoline scaffold, compound 8 presented higher trypanocidal activity against the epimastigote forms, while compound 22, against the trypomastigotes and amastigotes. Taken together, compounds 8 and 22 represent a promising scaffold for further development of trypanocidal compounds as drug candidates for treating Chagas disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rafaela Salgado Ferreira reports financial support was provided by Minas Gerais State Foundation of Support to the Research (FAPEMIG). Rafaela Salgado Ferreira reports financial support was provided by National Council for Scientific and Technological Development (CNPq). Rafaela Salgado Ferreira reports financial support was provided by Coordination of Higher Education Personnel Improvement (CAPES). Viviane Corrêa Santos reports financial support was provided by National Council for Scientific and Technological Development. Viviane Corrêa Santos reports financial support was provided by Coordination of Higher Education Personnel Improvement. Peter Kolb reports financial support was provided by German Research Foundation DFG. Rafaela Salgado Ferreira has patent #BR102022002935 pending to INPI - Instituto Nacional da Propriedade Industrial., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The high incidence of atrial arrhythmias in pulmonary hypertension (PH) might be associated with poor prognosis, and the left atrium (LA) may play a role in this. An important finding in PH studies is that LA remodeling is underestimated., Objective: This study investigated LA morphology and mechanical function, as well as the susceptibility to develop arrhythmias in a monocrotaline-induced PH (MCT-PH) model., Methods: Wistar rats aged 4 weeks received 50 mg/kg of MCT. Electrocardiography and histology analysis were performed to evaluate the establishment of the MCT-PH model. The tissue was mounted in an isolated organ bath to characterize the LA mechanical function., Results: Compared with the control group (CTRL), the MCT-PH model presented LA hypertrophy and changes in cardiac electrical activity, as evidenced by increased P wave duration, PR and QT interval in MCT-PH rats. In LA isolated from MCT-PH rats, no alteration in inotropism was observed; however, the time to peak contraction was delayed in the experimental MCT-PH group. Finally, there was no difference in arrhythmia susceptibility of LA from MCT-PH animals after the burst pacing protocol., Conclusion: The morphofunctional remodeling of the LA did not lead to increased susceptibility to ex vivo arrhythmia after application of the burst pacing protocol.

Objectives: One of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes., Methods: Male BALB/c mice were fed a chow or an HC diet for 8 wk., Results: Although differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation., Conclusion: Metabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Infrared thermography (IRT) is a non-invasive and efficient tool to detect changes in the animal's body surface temperature, which is directly associated with the animal's energy loss. Methane emission represents a significant energy loss, particularly in ruminants, as well as heat production. Therefore, the aim of this study was to correlate skin temperature measured using IRT with heat production (HP) and methane emission in lactating Holstein and crossbred ½ Holstein x ½ Gyr (Gyrolando-F1) cows. Six Gyrolando-F1 and four Holstein cows, all primiparous, at mid lactation were used to evaluate daily HP and methane emission using indirect calorimetry in respiratory chambers. Thermographic images were taken at anus, vulva, ribs (on the right side), left flank, right flank, right front foot, upper lip, masseter and eye; IRT was performed every hour during 8 h after the morning feeding. Cows received the same diet ad libitum. Daily methane emission was positively correlated with IRT taken at the right front foot 1 h after feeding in Gyrolando-F1 cows (r = 0.85, P < 0.05) and with IRT taken at the eye 5 h after feeding in Holstein cows (r = 0.88, P < 0.05). HP was positively correlated with IRT taken at the eye 6 h after feeding in Gyrolando-F1 cows (r = 0.85, P < 0.05) and with IRT taken at the eye 5 h after feeding in Holstein cows (r = 0.90, P < 0.05). Infrared thermography was positively correlated with HP and methane emission in both Holstein and Gyrolando-F1 lactating cows, although the anatomical points and times of image acquisition yielding the greatest correlation coefficients varies among breeds., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Introduced or invasive fish are susceptible to new parasites but can simultaneously carry infectious parasites from their native range towards new hosts. Screening these parasites is key to address the health of fish populations and spread of diseases., Methods: In this study, we sequenced a Coccidia parasite, for the first time from the blenny Omobranchus sewalli, introduced in the northern coast of Brazil with an Indo-Pacific origin., Results: Only one individual was infected, its genetic sequence matched (over 99%) with two lineages of undetermined species, belonging to the genus Goussia, sequenced from three marine fish species (Mulloidichthys flavolineatus, Lutjanus kasmira, and Selar crumenophthalmus) in Hawaii., Conclusions: Phylogenetic analysis suggests considerable differentiation between the Goussia detected and other Goussia spp. sequenced from North Atlantic marine fish, thus we cannot exclude the possibly that this parasite was carried by O. sewalli from its native Indo-Pacific range., (© 2023. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

To evaluate the prevalence of musculoskeletal ultrasonography (MSUS) abnormalities in asymptomatic elderly individuals. A cross-sectional controlled study was conducted and MSUS of 23 joints (wrist, metacarpophalangeal-MCP, proximal interphalangeal-PIP, elbow, glenohumeral, hip, knee, ankle, and metatarsophalangeal-MTP joints) was performed in healthy individuals aged 18-29 (young, n = 32) and 60-80 years-old (elderly, n = 32). Quantitative synovial hypertrophy (SH) was measured in mm and a semiquantitative scoring system (0-3) was used to grade SH, power doppler (PD) and bone erosion (BE). Young and elderly participants were 26.2 ± 3.2 and 65.9 ± 4.4 years-old, respectively. As compared to the young participants, elderly individuals had higher SH values in 35% of the joint surfaces (P < 0.05), higher rates of scores 1-3 for SH at the dorsal surface of the 3rd MCP, palmar surface of the 2nd MCP, 2nd PIP, 3rd MCP and 3rd PIP and subtalar joints (17.2 vs. 1.6%, P = 0.002; 29.7 vs. 6.3%, P = 0.001; 12.5 vs. 1.6%, P = 0.016; 21.9 vs. 6.3%, P = 0.011; 21.9 vs. 7.8%, P = 0.025; and 24.2 vs. 6.3%, P = 0.005, respectively), BE at the radiocarpal, ulnocarpal, dorsal surface of the 2nd MCP and posterior area of the glenohumeral joints (10.9 vs. 1.6%, P = 0.028; 12.5 vs. 0%, P = 0.003; 9.4 vs. 0%, P = 0.012; and 29.7 vs. 10.9%, P = 0.008, respectively) and PD at the dorsal surface of the 2nd and 3rd MCP joints (9.4 vs. 0%; P = 0.012 and 7.8 vs. 0%; P = 0.023, respectively). BE scores ≥ 1 were more frequent in the elderly (P < 0.05) in 22 (88%) of the joint surfaces evaluated. MSUS abnormalities are more frequent in asymptomatic elderly individuals as compared to young subjects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: TRPV1 desensitization or blockade promotes hyperthermia in rodents. Daily changes in core body temperature (Tc), spontaneous locomotor activity (SLA), and glucocorticoids are temporal cues for peripheral clocks. Thus, this study aimed to evaluate the effects of both desensitization and blockade of TRPV1 on Tc, SLA, blood corticosterone, and the clock genes Per1 and Bmal1 in the liver and adrenal., Methods and Results: Resiniferatoxin (RTX, 20 μg kg -1 ) known to desensitize the intra-abdominal TRPV1 channels was i. p. administered in adult male rats. One day after, RTX rats displayed higher Tc than vehicle rats (control) in the light and dark phases. RTX rats showed higher corticosterone at zeitgeber time (ZT) 6 and ZT12 compared to ZT0. Control rats showed a rise in corticosterone at ZT12. RTX abolished the Per1 peak in both the liver and adrenal glands, whereas it enhanced the peak of Bmal1 expression in the liver and decreased it in adrenal glands. Circadian variation in Tc and SLA was unaffected despite higher Tc being found along the light phase up to 5 days after RTX injection. Acute blockade of TRPV1 with the antagonist AMG-517 injected at ZT0 increased Tc and reduced corticosterone without affecting SLA. In the liver, while AMG-517 did not affect Per1, it increased Bmal1 mRNA. In adrenal glands, AMG-517 increased Per1 and did not affect Bmal1 expression. Although rats exposed to a 60-min 34 °C environment showed similar hyperthermia to that observed in AMG-517 rats, neither corticosterone nor liver nor adrenal clock genes changed., Conclusions: Inactivation of TRPV1 by abdominal desensitization or by antagonism alters the time-of-day changes of clock genes expression in the liver and adrenal, as well as corticosterone. TRPV1 may be necessary for signaling cyclical temporal cues for clock genes in the periphery but less critical for the circadian profile of Tc and SLA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maristela de Oliveira Poletini reports financial support was provided by Minas Gerais State Foundation of Support to the Research. Ana Maria de Lauro Castrucci reports financial support was provided by State of Sao Paulo Research Foundation. Frederico Sander Mansur Machado reports financial support was provided by National Council for Scientific and Technological Development. Nayara Abreu Coelho Horta reports financial support was provided by Coordination of Higher Education Personnel Improvement. Paola Fernandes reports financial support was provided by Coordination of Higher Education Personnel Improvement. Thais Santana R Cardoso reports financial support was provided by Coordination of Higher Education Personnel Improvement. Lucas Rios Drummond reports financial support was provided by Coordination of Higher Education Personnel Improvement. Candido Celso Coimbra reports financial support was provided by National Council for Scientific and Technological Development. Samuel P Wanner reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The role of suppressor of cytokine signaling 2 (SOCS2) in Aggregatibacter actinomycetemcomitans (Aa)-induced alveolar bone loss is unknown; thus, it was investigated in this study., Methods: Alveolar bone loss was induced by infecting C57BL/6 wild-type (WT) and Socs2-knockout (Socs2 -/- ) mice with Aa. Bone parameters, bone loss, bone cell counts, the expression of bone remodeling markers, and cytokine profile were evaluated by microtomography, histology, qPCR, and/or ELISA. Bone marrow cells (BMC) from WT and Socs2 -/- mice were differentiated in osteoblasts or osteoclasts for analysis of the expression of specific markers., Results: Socs2 -/- mice intrinsically exhibited irregular phenotypes in the maxillary bone and an increased number of osteoclasts. Upon Aa infection, SOCS2 deficiency resulted in the increased alveolar bone loss, despite decreased proinflammatory cytokine production, in comparison to the WT mice. In vitro, SOCS2 deficiency resulted in the increased osteoclasts formation, decreased expression of bone remodeling markers, and proinflammatory cytokines after Aa-LPS stimulus., Conclusions: Collectively, data suggest that SOCS2 is a regulator of Aa-induced alveolar bone loss by controlling the differentiation and activity of bone cells, and proinflammatory cytokines availability in the periodontal microenvironment and an important target for new therapeutic strategies. Thus, it can be helpful in preventing alveolar bone loss in periodontal inflammatory conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The objective of this study was to evaluate blood cells and metabolites, insulin-like growth factor-1 (IGF-1), digestibility, internal organs weight and histology, gene expression, and spleen cell proliferation of pre-weaned bull calves supplemented with a blend of essential oils in milk replacer (MR). Sixteen newborn Holstein × Gyr crossbred dairy bull calves, with body weight at birth of 33.3 ± 3.7 kg, were housed in individual sand bedded pens, blocked by genetic composition, and randomly assigned to 1 of 2 treatments in a randomized complete block design: Control (CON, n = 8) and blend of essential oils supplementation (BEO, n = 8, 1 g/day/calf, Apex Calf, Adisseo, China). The commercial blend was composed by plant extracts derived from anise, cinnamon, garlic, rosemary, and thyme. Animals were fed 5 L of MR/day reconstituted at 15% (dry matter basis), divided into two equal meals. Water and starter were provided ad libitum. ß-hydroxybutyrate, urea, and glucose were evaluated weekly, IGF-1 was evaluated biweekly, and total blood cell count was performed every four weeks until the end of the trial at eight weeks of age. Feed samples were collected three times a week and polled for weekly analysis. Apparent total nutrient digestibility was determined from d 56 to 60 of age. On d 60 ± 1, animals were euthanized for organ weight, histology, spleen cell proliferation, and intestinal gene expression analysis. Data were analyzed independently using linear mixed models using the REML method in the nlme package in R for continuous outcomes. A non-parametric test was used for ordered categorical outcomes using the Artools package in R. There were no differences between groups for blood evaluations, digestibility, gene expression, and a spleen cell proliferation assay. However, BEO calves presented a heavier pancreas, heavier intestines, bigger ileum villi, and higher cecum butyrate levels (P < 0.05), demonstrating that the EO supplementation helped intestinal development and symbiotic bacteria. It was also observed in CON animals' heavier respiratory tract and a higher eosinophil count (P < 0.05). Therefore, the organs where eosinophils are more active had a better response for BEO animals. No differences were found in the intestinal gene expression in the immune context. These results demonstrate that supplementing essential oils in MR could contribute to gut development and immune function. However, more research is needed to understand its impact on body development and define the best dosage and route of administration., (© 2023. The Author(s).)

This study evaluated the effect of crude protein (CP) reduction in four diets (156, 139, 132, and 127 g Kg -1 DM) maintaining constant metabolizable protein (188 g/day) on the follicular fluid and cumulus-oocyte complexes of mid-lactating Girolando cows. Twenty-two Girolando cows with average of 21.55 ±3.19 L daily milk yield, 105.30 ±22.62 days in lactation and 3.22 ±0.03 body condition score were selected. To reduce CP in diets and maintain constant metabolizable protein, urea and soybean meal were gradually replaced by lignosulfonate-treated soybean meal (SoyPass ® , Cargill), resulting in an increase in rumen-undegradable protein and a reduction in rumen degradable protein. A linear and quadratic reduction was observed in the plasma and follicular fluid urea nitrogen concentration following CP reduction, with the most intense reduction occurring in the 127 g Kg -1 DM group (p<0.001). As CP reduced, there was a tendency for a linear increase in the follicular growth rate (P=0.0696), on the number and proportion of viable oocytes (P<0.09), and also a linear increase for the number (P=0.0397) and proportion (P<0.09) of grade I viable oocytes. Plus, there was a linear effect for the number of cumulus oophorus cells. Cows fed with the lowest amount of CP had cumulus-oocyte complexes with higher numbers of cumulus oophorus cells (P=0.0238). Also, the reduction of diet crude protein was followed by a decrease in the probability of oocytes' DNA degradation. In conclusion, the reduction of CP in the diet of mid-lactating Girolando cows, reduces urea nitrogen concentration in both blood plasma and follicular fluid, and, as a consequence, increases the viability of oocytes and the number of cumulus oophorus cells while reducing oocytes' DNA degradation of follicular included cumulus-oocyte complex. The reduction on dietary CP may improve in vivo oocytes' embryo development impacting fertility of lactating dairy cows., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Background: Ionophore antibiotics improve the efficiency of energy metabolism, which has driven their use as a feed additive in ruminants for decades. Currently, they have not been approved in many countries, generating a challenge for the immediate search for plant extracts with a similar mode of action on rumen metabolism. This study evaluated the effects of enriched Prosopis juliflora (mesquite) piperidine alkaloid extract (MPA) levels as an alternative phytoadditive to sodium monensin (MON) in sheep., Results: The MPA diet did not differ from MON with regard to nutrient intake. A quadratic effect (P < 0.05) was observed for organic matter and neutral detergent fibre digestibility, with respective maximum point at 25.40 and minimum point at 0.95 mg kg -1 MPA. The MPA levels linearly decreased (P < 0.05) faecal nitrogen loss. MPA did not differ from MON with regard to nutrient digestibility, and MPA levels increased (P < 0.05) the proportion of digestible energy and metabolizability from dietary gross energy. The MPA levels linearly decreased (P < 0.05) enteric CH 4 production, the yield showing lower (P < 0.05) energy loss as CH 4 than MON., Conclusion: The results show that MPA levels of 17.3 and 27.8 mg kg -1 are enteric CH 4 inhibitors and enhance energy and protein utilization, indicating a promising alternative to MON for ruminants. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: to evaluate the effectiveness of triamcinolone Hexacetonide (TH) Intra-Articular Injection (IAI) in hand Interphalangeal Joints (IP) of Osteoarthritis (OA) patients to improve pain and joint swelling; improve function, goniometry, and grasping force, and assess IAI influence on radiographic evolution over 1-year., Methods: A randomized, double-blind study. 60 patients who underwent IAI at the most symptomatic IP joint were randomly assigned to receive TH+Lidocaine (LD) (TH/LD group) or just LD (LD group). Patients were assessed blindly for 1-year, at baseline and 1, 4, 8, 12, and 48 weeks. The following variables were assessed: articular pain and swelling, AUSCAN and COCHIN functional questionnaires, grip and pinch strength, goniometry, perception of improvement, acetaminophen consumption, and simple radiography. Repeated-measures ANOVA test was used to analyze the intervention response., Results: Sixty patients completed the follow-up. There were nine missed assessments. 97% were women; mean age of 61-years (SD = 8.2), and approximately 5-years of disease (SD = 3.6). Half of the patients present radiographic classification Kellgren and Lawrence (KL) grades I and II, and the other half grades III and IV. The two groups evolved similarly at 48-weeks. TH/LD group had a better evaluation in joint swelling and acetaminophen consumption (p = 0.04 and p < 0.001, respectively) at 48-weeks. Radiographically there was no statistical difference between groups (KL, p = 0.564; erosive OA, p = 0.999; worsening, p = 0.573)., Conclusion: The IAI IP hands OA is effective for the improvement of joint swelling and decrease of analgesic consumption and does not influence the radiographic evolution of the injected joint., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Omobranchus punctatus is native to the Indo-Pacific region and invasive in the Atlantic region, currently being considered one of the most widely distributed blenny species. However, recent molecular studies indicated that O. punctatus is a complex of species, with three divergent mtDNA lineages identified to date, stressing the need for a taxonomic revision. In this study, we used an integrative approach, combining morphological and genetic data, to shed light on the taxonomy and distribution of O. punctatus. Moreover, we provide the first genetic records of introduced populations in Brazil and discuss the introduction pattern of this species in this region. Morphological data shows that O. punctatus consists of at least five distinct and geographically restricted species: O. punctatus sensu stricto, O. dispar, O. sewalli, O. cf. kochi, and O. cf. japonicus. Species delimitation analyses performed using the mtDNA data available confirmed that O. punctatus sensu stricto, O. dispar and O. sewalli correspond to different species that started to diverge about 2.6 Mya. Furthermore, O. sewalli was identified as the invasive species colonizing Atlantic shores. The existence of historical oceanographic barriers, such as the emergence of the Sunda Shelf in the Eastern Indian Ocean during the Pleistocene, and the biological traits of these blennies are the most likely factors responsible for their genetic differentiation and subsequent speciation., (© 2022. The Author(s).)

The current COVID-19 pandemic has emphasized the vulnerability of communities living in the urban outskirts and informal settlements. The lack of reliable COVID-19 case data highlights the importance and application of wastewater-based epidemiology. This study aimed to monitor the COVID-19 trends in four vulnerable urban communities (slums and low-income neighborhoods) in metropolitan São Paulo by assessing the SARS-CoV-2 RNA viral load in wastewater. We analyzed 160 samples from May 2020 to June 2021 with weekly or fortnightly samplings. The samples were ultracentrifuged with glycine elution and quantified by N1/N2 SARS-CoV-2 RT-qPCR. The results of positivity were 100% (Paraisópolis, Heliópolis and Cidade Tiradentes) and 76.9% (Vila Brasilândia). The new case numbers of COVID-19, counted from the onset of symptoms, positively correlated with SARS-CoV-2 N1 viral loads from the two largest communities (p<0.001). SARS-CoV-2 infectivity was tested in Vero E6 cells after concentration with the two techniques, ultrafiltration (Centricon ® Plus-70 10 kDa) and sucrose cushion ultracentrifugation, but none of the evaluated samples presented positive results. Next-generation sequencing (NGS) analysis from samples collected in March and August 2021 revealed the presence of the clade 20 J (lineage P.1) belonging to the most prevalent circulating variant in the country. Our results showed that wastewater surveillance data can be used as complementary indicators to monitor the dynamics and temporal trends of COVID-19. The infectivity test results strengthened the evidence of low risk of infection associated with SARS-CoV-2 in wastewater.

The objectives of this study were: (1) to identify and rank phenotypically divergent animals for residual feed intake (RFI) regarding their efficiency (high: HE or low: LE); (2) to evaluate their relationships with ingestive behavior, ruminal and blood parameters, performance, and infrared thermography; and (3) to determine if such measurements can be used as feed efficiency markers in rearing dairy heifers. Thirty-eight heifers, 143 d ± 4 (Mean ± SD) of age and 108.7 kg ± 17.9 of body weight were used. The animals were fed with a total mixed ration during the 91 d of the trial. A phenotypic divergence of DMI for RFI was observed between -0.358 and 0.337 kg/d for HE and LE, respectively. Dry matter intake (DMI) was lower in the HE (2.5 kg DMI/d vs. 3.1 kg DMI/d), as was the number of visits to the feed bin with consumption (59 vs. 71). Feed intake was the best predictor of said divergence. Water intake and number of visits to the feed bin were presented moderate correlations with RFI. The ruminal fermentation variables, blood metabolites, blood hormones (such as the other ingestive behavior variables), and infrared thermography were not able to accurately predict HE or LE animals.

Chagas disease has a complex pathogenesis wherein the host immune response is essential for controlling its development. Suppressor of cytokine signaling(SOCS)2 is a crucial protein that regulates cytokine production. In this study, SOCS2 deficiency resulted in an initial imbalance of IL12- and IL-10-producing neutrophils and dendritic cells (DCs), which caused a long-lasting impact reducing inflammatory neutrophils and DCs, and tolerogenic DCs at the peak of acute disease. A reduced number of inflammatory and pro-resolving macrophages, and IL17A-producing CD4 + T cells, and increased lymphocyte apoptosis was found in SOCS2-deficient mice. Electrocardiogram analysis of chimeric mice showed that WT mice that received SOCS2 KO bone marrow transplantation presented increased heart dysfunction. Taken together, the results demonstrated that SOCS2 is a crucial regulator of the immune response during Trypanosoma cruzi infection, and suggest that a SOCS2 genetic polymorphism, or failure of its expression, may increase the susceptibility of cardiomyopathy development in Chagasic patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effects of bulk tank milk (BTM), WM, and PWM on the intake, ruminal parameters, blood parameters, health, and performance of dairy calves. Forty-five male crossbred dairy calves (Gyr × Holstein) were used. On their fourth day of age, animals were grouped according to body weight, serum protein levels, and genetic composition. Three treatments were assessed: BTM ( n = 15), WM from cows in antibiotic treatment ( n = 15), and PWM via high-temperature, short-time pasteurization (72-74 °C for 16 s) ( n = 15). During the experimental period (from 4 to 60 d of age), animals were fed 6 L of milk/d, divided into two equal meals. Water and concentrate were provided ad libitum . Daily measurements were made for milk, concentrate, and water intakes, as well as for fecal and respiratory scores. Rumen fluid and blood were sampled weekly. The following parameters were evaluated: volatile fatty acids (VFAs), pH and ammonia-N in rumen fluid, and β-hydroxybutyrate (BHB) and glucose in blood. Animals were weighed at birth, 4 d of age, and weekly up to 60 d of age. At the end of the experimental period (60 ± 1 d), all animals were euthanized for pulmonary evaluation. The randomized complete design with an interaction between treatment and week was the experimental method of choice for testing the hypothesis of the treatment's effect on all evaluated outcomes. Animals in the BTM treatment had higher milk dry matter intake (DMI), followed by WM and PWM calves. Concentrate DMI was lower for BTM in comparison to WM and PWM calves. However, total DMI showed no significant differences between treatments. The rumen fluid from calves receiving PWM had higher concentrations of acetate and propionate than that of BTM and WM animals. No differences were observed between treatments for blood glucose and BHB concentrations. Health parameters (fecal and respiratory scores) and pneumonia occurrence showed no significant difference between treatments. No differences were observed for average daily gain (ADG) or body growth. Feeding WM and PWM did not show significant negative effects on the intake, ruminal parameters, blood parameters, health, or performance of dairy calves.

The use of precision farming technologies, such as milking robots, automated calf feeders, wearable sensors, and others, has significantly increased in dairy operations over the last few years. The growing interest in farming technologies to reduce labor, maximize productivity, and increase profitability is becoming noticeable in several countries, including Brazil. Information regarding technology adoption, perception, and effectiveness in dairy farms could shed light on challenges that need to be addressed by scientific research and extension programs. The objective of this study was to characterize Brazilian dairy farms based on technology usage. Factors such as willingness to invest in precision technologies, adoption of sensor systems, farmer profile, farm characteristics, and production indexes were investigated in 378 dairy farms located in Brazil. A survey with 22 questions was developed and distributed via Google Forms from July 2018 to July 2020. The farms were then classified into seven clusters: (1) top yield farms; (2) medium-high yield, medium-tech; (3) medium yield and top high-tech; (4) medium yield and medium-tech; (5) young medium-low yield and low-tech; (6) elderly medium-low yield and low-tech; and (7) low-tech grazing. The most frequent technologies adopted by producers were milk meters systems (31.7%), milking parlor smart gate (14.5%), sensor systems to detect mastitis (8.4%), cow activity meter (7.1%), and body temperature (7.9%). Based on a scale containing numerical values (1-5), producers indicated "available technical support" (mean; σ 2 ) (4.55; 0.80) as the most important decision criterion involved in adopting technology, followed by "return on investment-ROI" (4.48; 0.80), "user-friendliness" (4.39; 0.88), "upfront investment cost" (4.36; 0.81), and "compatibility with farm management software" (4.2; 1.02). The most important factors precluding investment in precision dairy technologies were the need for investment in other sectors of the farm (36%), the uncertainty of ROI (24%), and lack of integration with other farm systems and software (11%). Farmers indicated that the most useful technologies were automatic milk meters systems (mean; σ 2 ) (4.05; 1.66), sensor systems for mastitis detection (4.00; 1.57), automatic feeding systems (3.50; 2.05), cow activity meter (3.45; 1.95), and in-line milk analyzers (3.45; 1.95). Overall, the concerns related to data integration, ROI, and user-friendliness of technologies are similar to those of dairy farms located in other countries. Increasing available technical support for sensing technology can have a positive impact on technology adoption.

The objectives of this study were: (1) to evaluate feed efficiency indexes and their relationships with body measurements and blood and ruminal metabolites in the pre-weaning period; (2) to determine if such measurements can be used as feed-efficiency markers during the pre-weaning period. Holstein-Gyr heifer calves ( n = 36), enrolled between 4 and 12 weeks of age, were classified into two residual feed intake (RFI) and residual body weight gain (RG) groups: high efficiency (HE; RFI, n = 10; and RG, n = 9), and low efficiency (LE; RFI, n = 10; and RG, n = 8). Calves were fed whole milk (6 L/day) and solid feed ad libitum. Body developments were measured weekly and feed intake (milk and solid feed) daily during the whole period. Blood samples were collected at 12 weeks of age and analyzed for glucose, insulin and β-hydroxybutyrate (BHB). Samples of ruminal content were collected on the same day and analyzed for pH, NH 3 -N, and volatile fatty acids (VFA). Among the growth characteristics, only the initial hip width differed between the RFI groups, and withers height differed between the RG groups. Concentration of BHB was greater and glucose: insulin ratios tended to be greater in LE-RG animals. Butyric acid proportions were similar among RFI groups, but tended to be greater for HE-RG than for LE-RG. Overall, correlation coefficients between RFI or RG and blood, rumen, or morphometric markers were low. Thus, it is unlikely that measurements of metabolic indicators, per se, will be useful in the early identification of more efficient animals. Understanding the underlying physiological basis for improved feed efficiency in dairy heifers requires further investigation.

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease., Methodology/principal Findings: C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 μg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 μg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue., Conclusions/significance: AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite., Competing Interests: The authors have declared that no competing interests exist.

Chagas disease is an important disease of the heart. Lipoxins have important regulatory functions in host immune response (IR). Herein, we examined whether the receptor for lipoxin A4, the formyl peptide receptor (FPR) 2, had an effect on Trypanosoma cruzi infection. In vitro, FPR2 deficiency or inhibition improved the activity of macrophages against T. cruzi. In vivo, during the acute phase, the absence of FPR2 reduced parasitemia and increased type 2 macrophages, type 2 neutrophils, and IL-10-producing dendritic cells. Moreover, the acquired IR was characterized by greater proportions of Th1/Th2/Treg, and IFNγ-producing CD8 + T cells, and reductions in Th17 and IL-17-producing CD8 + T cells. However, during the chronic phase, FPR2 deficient mice presented and increased inflammatory profile regarding innate and acquired IR cells (Th1/IFN-γ-producing CD8 + T cells). Notably, FPR2 deficiency resulted in increased myocarditis and impaired heart function. Collectively, our data suggested that FPR2 is important for the orchestration of IR and prevention of severe T. cruzi-induced disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To compare joint ultrasound measurements between the sexes in healthy volunteers. A cross-sectional study compared the joint ultrasound measurements between the sexes in healthy volunteers. Quantitative (synovial hypertrophy and perpendicular measurement in the largest synovial recess) and semiquantitative (synovial hypertrophy, power Doppler, and bone erosion; score 0-3) ultrasound measurements were performed. Forty-six articular recesses were evaluated and compared between group 1 (100 females) and group 2 (60 males) who were matched by age and BMI. For the quantitative measurements, 7360 recesses were studied. For the semiquantitative measurements, 22,720 recesses were evaluated. Higher values ( p  < .05) were found in females for the quantitative measurements of synovial hypertrophy for the following: radiocarpal, distal radioulnar and ulnocarpal, second/third dorsal and second/third palmar interphalangeal, second palmar metacarpophalangeal, glenohumeral, hip, talocrural, talonavicular, and talocalcaneal recesses; the highest difference was found for the hip (6.21 ± 1.35 vs. 4.81 ± 2.40) and distal radioulnar (1.46 ± 0.40 vs. 1.07 ± 0.70) recesses. For the semiquantitative measurements, significant differences were found. For synovial hypertrophy, higher measurements for females in the second/third palmar metacarpophalangeal, second palmar proximal interphalangeal, hip, tibiotalar, talonavicular, talocalcaneal, and second metatarsophalangeal recesses (highest difference for second palmar metacarpophalangeal [44 (22.0%) vs. 5 (4.2%)]). For power Doppler, there were higher values for females in the talonavicular recesses and higher values for males in the first/second/fifth metatarsophalangeal recesses (highest difference for fifth [9 (7.5%) vs. 2 (1.0%)]). For bone erosion, there were higher measurements for females in the radiocarpal recesses (10 [5.0%] vs. 0 [0.0%]) and higher values for males in the talonavicular recesses (4 [3.3%] vs. 0 [0.0%]). Higher quantitative and semiquantitative ultrasound measurements of synovial hypertrophy were typically found in females.

Chagas disease causes more deaths in the Americas than any other parasitic disease. Initially confined to the American continent, it is increasingly becoming a global health problem. In fact, it is considered to be an "exotic" disease in Europe, being virtually undiagnosed. Benznidazole, the only drug approved for treatment, effectively treats acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Previously, our research group demonstrated that 4-thiazolidinones presented anti-T. cruzi activity including in the in vivo assays in mice, making this fragment appealing for drug development. The present work reports the synthesis and anti-T. cruzi activities of a novel series of 4-thiazolidinones derivatives that resulted in an increased anti-T. cruzi activity in comparison to thiosemicarbazones intermediates. Compounds 2c, 2e, and 3a showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in mouse splenocytes. Besides, all the 2c, 2e, and 3a tested concentrations showed no cytotoxic activity on macrophages cell viability. When macrophages were submitted to T. cruzi infection and treated with 2c and 3a, compounds reduced the release of trypomastigote forms. Results also showed that the increased trypanocidal activity induced by 2c and 3a is independent of nitric oxide release. Flow cytometry assay showed that compound 2e was able to induce necrosis and apoptosis in trypomastigotes. Parasites treated with the compounds 2e, 3a, and 3c presented flagellum shortening, retraction and curvature of the parasite body, and extravasation of the internal content. Together, these data revealed a novel series of 4-thiazolidinones fragment-based compounds with potential effects against T. cruzi and lead-like characteristics., (Copyright © 2021 Elsevier B.V. All rights reserved.)