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Automated sensors have potential to standardize and expand the monitoring of insects across the globe. As one of the most scalable and fastest developing sensor technologies, we describe a framework for automated, image-based monitoring of nocturnal insects-from sensor development and field deployment to workflows for data processing and publishing. Sensors comprise a light to attract insects, a camera for collecting images and a computer for scheduling, data storage and processing. Metadata is important to describe sampling schedules that balance the capture of relevant ecological information against power and data storage limitations. Large data volumes of images from automated systems necessitate scalable and effective data processing. We describe computer vision approaches for the detection, tracking and classification of insects, including models built from existing aggregations of labelled insect images. Data from automated camera systems necessitate approaches that account for inherent biases. We advocate models that explicitly correct for bias in species occurrence or abundance estimates resulting from the imperfect detection of species or individuals present during sampling occasions. We propose ten priorities towards a step-change in automated monitoring of nocturnal insects, a vital task in the face of rapid biodiversity loss from global threats. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.
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Inteligencia Artificial , Insectos , Animales , Biodiversidad , Procesamiento de Imagen Asistido por Computador/métodos , Insectos/fisiologíaRESUMEN
BACKGROUND: Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses. RESULTS: The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation. CONCLUSIONS: The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus.
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The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever.
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Enfermedades de los Bovinos , Fiebre , Lactancia , Leche , Periodo Posparto , Reproducción , Excreción Vaginal , Animales , Bovinos , Femenino , Excreción Vaginal/veterinaria , Estudios Retrospectivos , Fiebre/veterinaria , Embarazo , Estudios de CohortesRESUMEN
Summary: Background. Bee venom allergy (BVA) can trigger local and systemic allergic reactions, including anaphylaxis. Recently, the molecular sensitization profile has gained importance in the reaction's stratification and venom immunotherapy (VIT). Methods. Retrospective analysis of patients with hypersensitivity to BVA, confirmed by specific sIgE to Apis mellifera ≥0.35 kU/L and/or positive skin tests to bee venom commercial extract, evaluated in specialized consultation. Demographic, clinical, and laboratory data (including molecular Api m 1, 4, and 10) were analyzed, looking for risk factors associated with the severity of the index reaction and reactions during VIT. Results. 93 patients were included (55.9% male; median age of 46 years), 57.3% with atopic comorbidities, and 23.4% with cardiovascular comorbidities. The median specific IgE to Apis mellifera was 6.7 kU/L (IQR 1.0-20.3) kU/L. Regarding the molecular profile, the median IgE to Api m 1 was 0.5 kU/L (57.5% positive out of all measurements); Api m 4 - 0.01 kU/L (11.9% positive), and Api m 10 - 0.3 kU/L (50.0% positive). No patient was monosensitized to Api m 4. The median age of the most severe sting reaction was 36 (IQR 26-48) years, with a median severity (Müeller scale) of 3 (IQR 2-3). Forty-seven patients (50.5%) underwent VIT, with 35.6% of reactions recorded. Allergic reactions during VIT were recorded in 35.6% of cases. The severity of the index reaction correlated positively with older ages (p=0.040; r=0.249), in contrast to monosensitization to Api m 1, which was an independent predictor of milder reactions (p=0.015). Sensitization to Api m 10 was associated with a higher likelihood of reactions during VIT (p=0.038) but potentially less systemic reactions at re-stings (p=0.097). Conclusions. Molecular sensitization profile appears to be relevant not only to the severity of index reactions but also during VIT. Studies of a large cohort of patients with molecular profiles are essential to validate these results and improve the clinical and therapeutic approach to BVA.
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OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.
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COVID-19 , Inflamasomas , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18 , Proteínas NLR , Colchicina/uso terapéutico , Interleucina-1beta/metabolismoRESUMEN
Osteoclasts play a key role in the regulation of bone mass and are highly active metabolically. Here we show that a metabolic reprogramming toward the hexosamine biosynthetic pathway (HBP) is required not only for osteoclast differentiation but also to determine the bone resorption mode during physiological and pathological bone remodeling. We found that pharmacological inhibition of O-GlcNAc transferase (OGT) significantly reduced protein O-GlcNAcylation and osteoclast differentiation. Accordingly, genetic deletion of OGT also inhibited osteoclast formation and downregulated critical markers related to osteoclasts differentiation and function (NFATc1, αvintegrin, cathepsin K). Indeed, cells treated with OSMI-1, an OGT inhibitor, also reduced nuclear translocation of NFATc1. Furthermore, the addition of exogenous N-acetylglucosamine (GlcNAc) strongly increased osteoclast formation and demineralization ability. Strikingly, our data show for the first time that O-GlcNAcylation facilitates an aggressive trench resorption mode in human cells. The incubation of osteoclasts with exogenous GlcNAc increases the percentage of erosion by trench while having no effect on pit resorption mode. Through time-lapse recording, we documented that osteoclasts making trenches moving across the bone surface are sensitive to GlcNAcylation. Finally, osteoclast-specific Ogt-deficient mice show increased bone density and reduced inflammation-induced bone loss during apical periodontitis model. We show that osteoclast-specific Ogt-deficient mice are less susceptible to develop bacterial-induced periapical lesion. Consistent with this, Ogt-deleted mice showed a decreased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site. In summary, here we describe a hitherto undiscovered role of the HBP/O-GlcNAcylation axis tuning resorption mode and dictating bone resorption outcome.
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Resorción Ósea , Periodontitis Periapical , Ratones , Humanos , Animales , Hexosaminas/metabolismo , Vías Biosintéticas , Resorción Ósea/metabolismo , Osteoclastos/metabolismo , Factores de Transcripción/metabolismoRESUMEN
We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.
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Antioxidantes , Sepsis , Animales , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Teorema de Bayes , Quimiocinas , Creatinina , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Modelos Teóricos , Insuficiencia Multiorgánica/tratamiento farmacológico , Riboflavina/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , UreaRESUMEN
Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats. Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO2 -) and thiobarbituric acid reactive species (TBARS) levels were determined. Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis. Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms.
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Summary: Rapid drug desensitization (RDD) is a procedure performed when no alternative drug is considered equally effective. The aim of our study is to describe the experience with RDD to cytostatics in patients being treated for gynaecological cancer in a tertiary hospital, over a period of 5 years. In this paper, we review 22 cases and 107 episodes of RDD; 86.3% of patients had advanced disease and the mortality rate at the time of data collection was 50.0%. RDD was performed on 81.8% patients for platinum, 13.6% for taxanes, and 4.5% for anthracyclines. The reintroduction of antineoplastic drugs in all patients with a previous history of immediate hypersensitivity reaction demonstrated the safety and efficacy of this procedure. There was serious complication (anaphylaxis) in only one case.
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Hipersensibilidad a las Drogas , Neoplasias , Humanos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , Centros de Atención Terciaria , Desensibilización Inmunológica/métodos , Taxoides/efectos adversos , Neoplasias/inducido químicamente , Neoplasias/tratamiento farmacológicoRESUMEN
We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.
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PURPOSE: The oral care of a child with autism spectrum disorders (ASD) is a challenge, not only for dentists, but also for parents. The objective of this study was to evaluate the difficulties encountered by parents in maintaining oral hygiene in autistic children and the solutions they found to facilitate this daily act. METHODS: A questionnaire with closed and open questions about characteristics of the child and oral health at home, conducted via Google Form, was sent to French families through 301 associations of parents with autistic children. For the quantitative analysis, logistic regression was used. The open answers were analysed by theme. RESULTS: This study included 756 offspring aged 14.4 (± 8.1) years. Girls were 1.7 (95% CI: 1.1-2.8) times more likely to have toothbrushing difficulty than boys. Nonverbal patients (OR:3.2; 95% CI: 2.2-4.9), autistic patients (OR:2.8; 95% CI: 1.4-5.2), patients using pictograms (OR:1.6; 95% CI: 1.1-2.4), and younger children (OR:0.9; 95% CI: 0.9-0.9) were significantly more likely to encounter difficulties in tolerating toothbrushing. The qualitative analysis showed that parents used three main ways to facilitate toothbrushing: planning, modelling and making it enjoyable. Seventy-nine percent of parents did not feel sufficiently informed about the different oral hygiene prevention tools and techniques for their ASD children and would like to be educated in the daily management of oral hygiene. CONCLUSION: The role of parents remains essential and professionals should work in collaboration with them.
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Trastorno del Espectro Autista , Cepillado Dental , Femenino , Humanos , Masculino , Salud Bucal , Higiene Bucal , PadresRESUMEN
The objective was to investigate the economic effect of treating dairy cows with metritis using ceftiofur-free acid or leaving them untreated at the time of diagnosis. Cows with a fetid, watery, red-brownish vaginal discharge were diagnosed with metritis (d 0). Data from 875 dairy cows (506 primiparous and 369 multiparous) from 1 herd in northern Florida that had been part of a larger study evaluating different treatments for metritis were used for the economic analysis. Holstein cows with metritis had been randomly assigned to: Ceftiofur (CEF, n = 239) = subcutaneous injection of 6.6 mg/kg of ceftiofur crystalline-free acid in the base of the ear at d 0 and d 3; Untreated (UNT, n = 233) = no treatment applied at metritis diagnosis. Both groups could receive escape therapy if condition worsened. A group of nonmetritic healthy cows (NMET; n = 403) from the same cohort was randomly selected for comparison. Continuous outcomes such as 300-d milk production (kg/cow), milk sales ($/cow), cow sales ($/cow), treatment cost by 60 days in milk ($/cow), reproduction cost ($/cow), replacement cost ($/cow), feeding cost ($/cow), and gross profit per cow ($/cow) were analyzed using the ANOVA (MIXED procedure of SAS version 9.4). Dichotomous outcomes such as pregnancy and culling by 300 d were analyzed using logistic regression (GLIMMIX procedure of SAS). Models included the fixed effects of treatment, parity, and the interaction between treatment and parity. A stochastic analysis was performed with 10,000 iterations using the observed results from each group. The CEF treatment resulted in greater treatment cost by 60 DIM than UNT ($112 vs. $37), but resulted in a greater proportion of pregnant cows (71 vs. 61%) and decreased culling by 300 DIM (29 vs. 39%) compared with UNT. Gross profit was lesser for UNT than NMET ($2,969 vs. $3,426), and CEF was intermediate ($3,219). The stochastic analysis showed that the mean difference in gross profit between UNT and NMET was -$457; saleable milk (49%) and replacement cost (24%) accounted for most of the variation. The mean difference in gross profit between CEF and NMET group was -$207; saleable milk (82%) and initial metritis treatment cost (9%) accounted for most of the variation. The mean difference in gross profit between the UNT and the CEF group was -$250; replacement cost (41%) and cow sales (31%) accounted for most of the variation. In summary, metritis caused large economic losses when left untreated, and CEF reduced those losses by improving fertility, reducing culling and replacement cost, and reducing milk yield losses.
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Enfermedades de los Bovinos , Endometritis , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Endometritis/tratamiento farmacológico , Endometritis/veterinaria , Femenino , Florida , Lactancia , Leche , Paridad , Periodo Posparto , Embarazo , ReproducciónRESUMEN
The objective of this study was to estimate the cost of metritis in dairy herds. Data from 11,733 dairy cows from 16 different farms located in 4 different regions of the United States were compiled for up to 305 d in milk, and 11,581 cows (2,907 with and 8,674 without metritis) were used for this study. Metritis was defined as fetid, watery, red-brownish vaginal discharge that occurs ≤21 d in milk. Continuous outcomes such as 305-d milk production, milk sales ($/cow), cow sales ($/cow), metritis treatment costs ($/cow), replacement costs ($/cow), reproduction costs ($/cow), feeding costs ($/cow), and gross profit per cow ($/cow) were analyzed using mixed effect models using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). Gross profit was also compared using the Kruskal-Wallis test. Dichotomous outcomes such as pregnant and culling by 305 d in milk were analyzed using the GLIMMIX procedure of SAS. Time to pregnancy and culling were analyzed using the PHREG procedure of SAS. Models included the fixed effects of metritis, parity, and the interaction between metritis and parity, and farm as the random effect. Variables were considered significant when P ≤ 0.05. Metritis cost was calculated by subtracting the gross profit of cows with metritis from the gross profit of cows without metritis. A stochastic analysis was performed with 10,000 iterations using the observed results from each group. Milk yield and proportion of cows pregnant were lesser for cows with metritis than for cows without metritis, whereas the proportion of cows leaving the herd was greater for cows with metritis than for cows without metritis. Milk sales, feeding costs, residual cow value, and gross profit were lesser for cows with metritis than for cows without metritis. Cow sales and replacement costs were greater for cows with metritis than for cows without metritis. The mean cost of metritis from the study herds was $511 and the median was $398. The stochastic analysis showed that the mean cost of a case of metritis was $513, with 95% of the scenarios ranging from $240 to $884, and that milk price, treatment cost, replacement cost, and feed cost explained 59%, 19%, 12%, and 7%, respectively, of the total variation in cash flow differences. In conclusion, metritis caused large economic losses to dairy herds by decreasing milk production, reproduction, and survival in the herd.
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Enfermedades de los Bovinos , Industria Lechera , Animales , Bovinos , Femenino , Lactancia , Leche , Paridad , Embarazo , ReproducciónRESUMEN
While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG35-55. EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis.
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Antiinflamatorios/farmacología , Diferenciación Celular/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/prevención & control , Ácido Mevalónico/metabolismo , Quinolinas/farmacología , Médula Espinal/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Animales , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Mediadores de Inflamación/metabolismo , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Masculino , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Péptidos , Médula Espinal/inmunología , Médula Espinal/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
The published online version contains figure in poor quality.
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Neoplasias de Cabeza y Cuello , Sobrevivientes , Terapia por Ejercicio , Humanos , Calidad de VidaRESUMEN
Beer-Lambert-Bouguer law is for a limiting case and, therefore, it is not useful to describe the relationship between absorption signal and enantiomer concentration in a stream when there are nonlinear phenomena present. In this work, the Chiral Detector (CD-2095 JASCO) equipment was used to measure simultaneously the UV-Vis and circular dichroism (CD) signals of a stream with different compositions of praziquantel enantiomers. The tested models were calibrated (parameter estimation) and validated using the Leave-One-Out Cross Validation (LOOCV) method. Both UV-vis and CD signals were absorbed differently in mixtures in comparison to pure solutions, indicating a nonlinear relationship between the absorbed signal and the enantiomer concentration in a mixture stream. Empirical mathematical relationships were tested for each signal (UV-vis and CD) and the pair of equations was evaluated using the Mean Square Error (MSE) metric for each enantiomer concentration (MSEL and MSED) and the pair of equations with the smallest MSEt (=MSEL + MSED) metric was chosen. Confidence interval analysis helped to find even simpler equations in comparison to the chosen ones. Higher nonlinearity was observed for a mixture with low L-PZQ concentration. The developed methodology allowed the choice of an empiric model to give good predictions in a wide range of concentration, what is of utmost importance for monitoring and automatic control purposes, for instance.
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Praziquantel , Dicroismo Circular , EstereoisomerismoRESUMEN
The main objective of this study was to evaluate the efficacy of intrauterine administration of chitosan microparticles (CM) in curing metritis in dairy cows. A secondary objective was to evaluate the effects of metritis treatments on milk yield, survival, and reproductive performance. Cows with a fetid, watery, red-brownish vaginal discharge were diagnosed with metritis. Holstein cows (n = 826) with metritis from 3 dairies located in northern Florida were blocked by parity (primiparous or multiparous) and, within each block, randomly assigned to one of 3 treatments: CM (n = 276) = intrauterine infusion of 24 g of CM dissolved in 40 mL of sterile distilled water at the time of metritis diagnosis (d 0), 2 (d 2), and 4 (d 4) d later; ceftiofur (CEF; n = 275) = subcutaneous injection of 6.6 mg/kg ceftiofur crystalline-free acid in the base of the ear at d 0 and d 3; Control (CON; n = 275) = no treatment applied at metritis diagnosis. All groups could receive escape therapy if condition worsened. Cure was considered when vaginal discharge became mucoid and not fetid. A group of nonmetritic (NMET; n = 2,436) cows was used for comparison. Data were analyzed by generalized linear mixed and Cox's proportional hazard models. Cows in CM and CON had lesser risk of metritis cure on d 12 than cows in CEF (58.6 ± 5.0 vs. 61.9 ± 4.9% vs. 77.9 ± 3.9, respectively). The proportion of cows culled within 60 days in milk (DIM) was greater for cows in CM than for cows in CEF and CON (21.5 ± 2.7 vs. 9.7 ± 1.9 vs. 11.3 ± 2.0%, respectively). Treatment did not affect rectal temperature or plasma nonesterified fatty acids, ß-hydroxybutyrate, and haptoglobin concentrations. Milk yield in the first 60 DIM differed for all treatments, and it was lowest for CM (35.8 ± 0.3 kg/d), followed by CON (36.8 ± 0.3 kg/d) and CEF (37.9 ± 0.3 kg/d). The hazard of pregnancy up to 300 DIM was lesser for CM than CEF (hazard ratio = 0.62; 95% CI: 0.50-0.76), for CM than CON (hazard ratio = 0.77; 95% CI: 0.62-0.95) and for CON than CEF (hazard ratio = 0.80; 95% CI: 0.65-0.99). Culling was greater, and milk yield and fertility were lesser for CEF than NMET. In summary, CM did not improve the cure of metritis, and was detrimental to milk yield, survival, and fertility compared with CON. In contrast, CEF increased the cure of metritis, milk yield, and fertility compared with CM and CON. Finally, the negative effects of metritis on milk yield culling and fertility could not be completely reversed by CEF.