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Background: Tear film (TF) helps maintain and protect ocular function against damage to the ocular surface. Proteins are one of its main constituents, whose expression pattern can be used as a biomarker of ocular changes and systemic diseases. The aim of this study was to evaluate the expression of proteins in the TF of domestic cats before and after infection with Toxoplasma gondii, in the phases of acute infection and chronicity. Twelve healthy cats received orally homogenized brain matter obtained from mice inoculated with T. gondii oocysts, strain ME49. Cat feces were collected daily from the third day after infection to assess the release of oocysts. TF samples were obtained from cats, by Schirmer's Tear Test 1, on day 0 (before infection), day 5 after infection (acute phase of infection, with maximum peak release of oocysts in feces) and on day 21 after infection (start of chronic phase, 7 days after total absence of oocyst release in feces). Tear samples were also submitted to proteomic analysis in a Q-Tof-Premier mass spectrometer., Results: A total of 37 proteins with scores equal to or greater than 100 were identified on D0, followed by 36 on D5 and 42 on D21. Of these, 27 were common to D0 and D5, 33 to D0 and D21, 27 to D5 and D21, and 26 were common to the three groups, totaling 54 proteins. The most abundant proteins were lipocalin allergen Fel d, serum albumin, aldehyde dehydrogenase, lactoperoxidase and lactotransferrin. There was no significant difference in the abundance of proteins found on D0 and D5, but there was a statistical difference between D0 and D21 for ACT1_AEDAE, CERU_HUMAN and GELS_HUMAN. Regarding D5 and D21, there were significant differences for KV1_CANLF, LAC_PIG, TRFL_PIG, ACT1_AEDAE, CERU_HUMAN, GELS_HUMAN and OVOS2_HUMAN., Conclusions: The main proteins identified in the TF of domestic cats are similar to those found in humans and other animal species. Most are part of the ocular surface defense system against injuries. The most expressed proteins in animals in the chronic phase of T. gondii infection are associated with the immune response to the parasite., (© 2021. The Author(s).)

The aim of this study was to investigate the proteins found in tear film of healthy domestic cats. Schirmer tear test strips were used to collect tear samples of twelve healthy cats, which were mixed, centrifuged, and placed in a single 1.5 mL microtube that was frozen at -20°C, until analysis by two-dimensional polyacrylamide gel and mass spectrometry associated with high-performance liquid chromatography. The resulting spectra were analyzed and compared with the Swiss-Prot search tool. Forty peptides were detected in the analyzed protein fragments of 90 spots, with 16 proteins identified. Of these, the authors confirmed what has been already found in other studies: lactotransferrin, serum albumin, allergenic lipocalins, and neutrophil gelatinase-associated lipocalin. Others were considered novel in tear film samples of all species: cyclin-dependent protein kinase, serine/arginine repetitive matrix protein, apelin receptor, secretory protein related to C1q/TNF, Wee1, α -1,4 glucan phosphorylase, and WD repeat domain 1. The network was divided into 11 clusters, and a biological function was assigned. Most of the proteins have functions in the defense and maintenance of feline ocular surface homeostasis. Serum albumin is a bottleneck protein, with a high betweenness value. This paper is a pioneer in reporting, in-depth, the tear film proteome of domestic cats., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Jéssica Fontes Veloso et al.)

Neutrophils respond differently to violations of the body's physiological barriers during infections. Extracellular traps comprise one of the mechanisms used by these cells to reduce the spread of pathogens to neighboring tissues, as well as ensure a high concentration of antimicrobial agents at the site of infection. To date, this innate defense mechanism has not been previously demonstrated in neutrophils of cats exposed to Toxoplasma gondii. The aim of this study was to characterize the in vitro release of neutrophil extracellular traps (NETs) when neutrophils isolated from cats were exposed to T. gondii. First, cellular viability was tested at different time points after parasite exposure. The production of reactive oxygen species (ROS) and lactate dehydrogenase and the amount of extracellular DNA were quantified. In addition, the number of parasites associated with neutrophils was determined, and the observed NETs formed were microscopically characterized. Results showed that (i) in culture, neutrophils isolated from cats presented diminished cellular viability after 4 h of incubation, and when neutrophils were incubated with T. gondii, they displayed cytotoxic effects after 3 h of interaction; (ii) neutrophils were able to release structures composed of DNA and histones, characterized as NETs under optical, immunofluorescence, and electron scanning microscopy, when stimulated with T. gondii; (iii) only 11.4% of neutrophils were able to discharge NETs during 3 h of incubation; however, it was observed through extracellular quantification of DNA that this small number of cells were able to display different behavior compared to a negative control (no parasite) group; (iv) significant differences in ROS production were observed in neutrophils exposed to T. gondii. In conclusion, our results showed that neutrophils isolated from cats exposed to T. gondii release structures composed of DNA and histones, similar to what has already been described in other neutrophil species infected with the parasite., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to determine the frequency and factors associated with Toxoplasma gondii in naturally infected equids in northeastern Brazil. Serum samples from 569 equids (528 horses, 8 mules and 33 donkeys) were subjected to the indirect fluorescent antibody test. Generalized linear models were used to evaluate associated factors. Among the 569 animals sampled, 118 (30.6%) living in rural areas and 14 (26.42%) in urban areas were seropositive (p>0.05). Seropositive animals were observed on 95% of the farms and in all the municipalities. Donkeys/mules as the host, presence of domestic cats and rats on the farm, ingestion of lagoon water and goat rearing remained in the final model as factors associated with infection. Preventive measures such as avoiding the presence of domestic cats close to rearing areas, pastures and sources of water for the animals should be adopted. The wide-ranging distribution of positive animals also indicated that infection in other domestic animals and in humans, through the contaminated environment, was possible. It should be highlighted that there was the possibility that donkeys and mules would continue to have detectable titers for longer, thus explaining the prevalence found. Further studies are needed to confirm this possibility.

The aim of this study was to determine the frequency and factors associated to Babesia caballi, Theileria equi and Trypanosoma evansi in naturally infected equids from the northeast Brazil. Blood samples from 569 equids (528 horses, 8 mules, and 33 donkeys) were collected and tested for the presence of DNA of each of these protozoan parasites by PCR. Generalized linear models were used to evaluate risk factors associated with the infection. The frequency of T. equi infection was 83.5% (475/569) - 84.3% in horses, and 73.2% in donkeys and mules. The results of the final model indicated that age (senior group) and animal species (mule and donkey group) were protective factors against this pathogen. The frequency of B. caballi infection was 24.3% (138/569) - 23.5% in horses and 34.1% in donkeys and mules. Age (adult and senior group) was considered a protective factor against B. caballi infection whereas animal species (donkey and mule group) were considered a risk factor for the infection. Trypanosoma evansi infection was not detected in any of animals. Our results suggest that equids from the area studied may be infected earlier in life with the etiological agents of equine piroplasmosis and become asymptomatic carriers.

Purpose: Osimertinib was initially approved for T790M-positive non-small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR -mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described., Experimental Design: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients., Results: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as potential resistance drivers. Alterations of cell-cycle genes were associated with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P = 0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second PFS (PFS2) of 12.6 months; 21 patients received local consolidation radiation with a median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared with discontinuation (11.2 vs. 6.1 months, P = 0.02)., Conclusions: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients. See related commentary by Devarakonda and Govindan, p. 6112 ., (©2018 American Association for Cancer Research.)

This study aimed to determine the prevalence, factors associated, laboratory findings (with and without coinfection by retroviruses) among naturally infected cats by hemoplasmas in northeastern Brazil. For convenience, 200 domesticated and healthy cats were selected. Blood samples were taken to perform complete blood counts, serum biochemical, immunochromatography tests and nPCR for FIV and FeLV, and PCR for hemoplasma recognition. An interview was conducted to determine the factors associated with hemoplasmas. A total of 71/200 (35.5%) cats were positive for at least one hemoplasma species. Isolated infections were observed in 12,5% for 'Candidatus Mycoplasma haemominutum', 12% for Mycoplasma haemofelis and 3% for 'Candidatus Mycoplasma turicensis'. Regarding copositivity, 2% of the animals were positive for M. haemofelis and 'Candidatus Mycoplasma haemominutum', 1.5% for M. haemofelis and 'Candidatus Mycoplasma turicensis', and 4.5% for ' Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis'. No clinical and laboratory changes were observed in the animals that were concomitantly positive for retroviruses and hemoplasmas. Periurban region cats were more likely to be infected by M. haemofelis, while contact with other cats and infection by ' Candidatus Mycoplasma turicensis' were associated with 'Candidatus Mycoplasma haemominutum'. This study indicates that infection by hemoplasmas is a common find in cats from northeastern Brazil.

We aimed to evaluate the effects of maternal nutrition (MN) and foetal sex on the intestinal development of bovine foetuses throughout different days of gestation (DG). Forty-four multiparous, dry Holstein × Gyr cows with average initial body weight of 480 ± 10 kg were fed the same diet of either restricted feeding at 1.15% of body weight (CO, n = 24) or fed ad libitum (overnourished, ON, n = 20). Six cows from CO group and five cows from ON group were slaughtered at 139, 199, 241 and 268 DG, and foetuses were necropsied to evaluate the intestinal development. The mass, length and density of foetal intestines were not affected by MN (p ≥ 0.260). An interaction between MN and DG was observed for the villi length of jejunum (p = 0.006) and ileum (p < 0.001). Villi length of jejunum and ileum was higher (p < 0.10) in foetuses from ON-fed cows than in foetuses from CO-fed cows at 139 DG. However, at 199 DG, the villi length of jejunum and ileum of foetuses from CO-fed cows was higher than in foetuses from ON-fed cows. Despite these differences, MN did not affect the villi length of jejunum and ileum at 268 DG (p > 0.10). Female foetuses had greater small intestine mass (p = 0.093), large intestine mass (p = 0.022), small intestine mass in proportion to body mass (p = 0.017) and large intestine mass in proportion to body mass (p < 0.001) than male foetuses. Female foetuses had also longer small intestine (p = 0.077) and greater small intestine density (p = 0.021) and villi length of jejunum (p = 0.001) and ileum (p = 0.010) than males. We conclude that MN affects the pathway for the development of foetal villi length throughout the gestation in bovine foetuses without changing the final villi length. Female foetuses had higher intestinal mass, density and villi length than males during the foetal phase in bovines., (Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.)

Our aims were to determine the frequencies of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in owned and stray cats in the northeastern region of Brazil, ascertain the status of FeLV infection, and investigate potential associated factors among the owned cats. Blood samples from 200 asymptomatic owned cats and 30 stray cats were processed using nested PCR and commercial immunochromatographic tests to diagnose infections. To evaluate the factors associated with FIV and/or FeLV in owned cats, a semi-structured interview was conducted with each owner about the animal's environment, and these data were subjected to unconditional logistic regression. The frequencies for owned cats were 6% (12/200) and 3% (6/200) for FIV and FeLV, respectively. No owned cat was positive for both viruses. Stray cats showed frequencies of 6.66% (2/30) and 0% (0/30) for FIV and FeLV, respectively. Contact with other cats and living in peri-urban areas were considered to be risk factors (P < 0.05) for FIV. We did not identify any factors associated with infections with FeLV. Our results confirm the presence of these two retroviruses in the region under study. Our use of different diagnostic techniques allowed us to determine the frequency of retroviruses in the feline population more accurately, particularly with regard to infections by FeLV, which have complex pathogenesis.

The aim of this study was to determine the frequency and the factors associated with infection by Toxoplasma gondii and demonstrate occurrences of coinfection with Neospora caninum, the feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in cats in the state of Bahia, Brazil. A total of 231 blood samples were collected from 201 owned cats and 30 stray cats. Serological investigations on T. gondii and N. caninum were performed using the indirect fluorescent antibody test with cutoff points of 1:64 and 1:50, respectively. To diagnose FIV and FeLV, a commercial immunochromatographic kit and a nested polymerase chain reaction (PCR) was used. Unconditional logistic regression was performed to assess the factors associated with infection by T. gondii among owned cats. The seropositivity for T. gondii among the owned cats and stray cats was 44.3% (89/201) and 53.3% (16/30), respectively. For N. caninum, the seropositivity among owned cats was 21.4% (43/201) and among stray cats, 23.3% (7/30). The copositivity between the two coccidia were 23.6% (21/201) and 37.5% (6/30), among owned and stray cats respectively. The periurban environment was a risk factor for infection by T. gondii, while infection by FIV was associated with infection by T. gondii (p<0.05) among owned cats. No association was found between T. gondii and FeLV, or between N. caninum and the retroviruses. Based on these results, it can be concluded that the cats of the present study were exposed to the agents T. gondii and N. caninum, which suggests that significant infection of intermediate hosts and or environmental contamination with oocysts was present, and that the cats coinfected with T. gondii and the retroviruses did not present any serological signs of reactivation of infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To evaluate the functional results from patients with surgical fractures in the thoracolumbar spine., Method: A prospective study including 100 patients with spinal fractures in the thoracic and lumbar segments was conducted. The lesions were classified in accordance with the AO system, and the patients were treated surgically. The presence of early kyphosis and its evolution after the surgical intervention, and the presence of postoperative pain and its evolution up to the 24(th) week after the surgery, were evaluated. We compared our data with the literature., Results: One hundred surgical patients were analyzed, of which 37 were type A, 46 were type B and 17 were Type C. Patients who presented Frankel A kept their clinical status, but patients with Frankel B or higher evolved with some improvement. The average improvement in pain based on a visual analog scale was more than four points. All the patients were able to return to their daily routine activities, although we did not take the return to work to be an assessment criterion., Conclusion: Despite controversy regarding the indications for surgery in cases of fractured spine, we believe that the method that we used was satisfactory because of the good results and low complication rate. However, more randomized prospective studies with longer follow-up are needed in order to evaluate this type of fixation.

Poly(methylmetacrilate)-maghemite (PMMA-gamma-Fe2O3) hybrid material was studied by the electron stimulated ion desorption (ESID) techniques coupled with time-of-flight mass spectrometry (TOF-MS) and theoretical investigation about its fragmentation. Moreover, atomic force microscopy was utilized to characterize the morphology before and after ionic desorption. ESID results indicated differences of pattern fragmentation for different compositions of hybrid material in comparison with neat PMMA. Theoretical studies suggest that kinetics effects can take place in the fragmentation process and electrostatic contributions were important in the stabilization of PMMA on maghemite after the grafting process., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To verify whether spinal surgery causes relevant changes in the blood clotting process and define which factors have the greatest influence on changes found., Method: This is a not randomized, cross-sectional study, Forty seven patients were evaluated between August 2011 and February 2013, whose clinical, surgical, laboratory and image daata were collected. The data obtained were crossed with the epidemiological data of each patient in a moment prior to and another after surgery searching which variables have been directly influenced., Result: Our analysis showed that the most important changes occurred in patients with BMI classified, according to the World Health Organization (WHO) as out of healthy range. Other smaller correlations were also found. Another important consideration was the tendency to observe hypercoagulability in smoker patients, a fact that is not influenced by spinal procedures., Conclusion: We concluded that spinal surgeries cause few relevant changes in the blood clotting process and that among the factors studied, BMI (when out of the healthy range, according to the WHO classification) showed closer relationship with changes in laboratory coagulation tests. Level of Evidence III, Cross-Sectional Study.

Drug interaction is a clinical event in which the effects of a drug are altered by the presence of another drug, phytochemical drug, food, beverage, or any environmental chemical agent. The incidence of adverse reactions caused by drug interactions is unknown. This lack of information is compounded by not knowing the number of patients who are prescribed combinations of drugs that can potentially interact. Patients who will or will not experience an adverse drug interaction cannot be clearly identified. Those with multiple diseases, with kidney or liver dysfunction, and those on many drugs are likely to be the most susceptible. Patients with autoimmune diseases are at higher risk for drug interactions. In addition to representing a risk for the patient and jeopardizing the health care provided by professionals, drug interactions can increase dramatically health care costs. This review article approached the clinically relevant interactions between the most used drugs in rheumatology (except for non-steroidal anti-inflammatories and corticosteroids) aiming at helping rheumatologists to pharmacologically interfere in the disease processes, in the search for better outcomes for patients and lower costs with the complex therapy of chronic diseases they deal with.