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The 2 brown seaweeds, Fucus serratus and Fucus vesiculosus, have demonstrated anti-methanogenic properties in vitro with reductions in CH4 production ranging from 53 to 63%. This study aimed to investigate the effects of the 2 Fucus seaweeds on enteric CH4 emissions, DMI, ECM, and nutrient digestibility when fed to dairy cows. The experiment was conducted using 4 multi-cannulated lactating Danish Holstein dairy cows, which over 3 experimental periods received either: 1) basal diet (CON; diet without any seaweed), 2) basal diet diluted with 4% (DM basis) Fucus serratus (SER), or 3) basal diet diluted with 4% (DM basis) Fucus vesiculosus (VES); resulting in one complete 3 × 3 Latin square and one incomplete 3 × 3 Latin square. Each period lasted 21 d and consisted of 14 d of adaptation, followed by 3 d of digesta sampling, and 4 d of gas exchange measurements using respiration chambers. Milk yield and feed intake were recorded daily. Blood samples were collected on d 15 and 17. All parameters were statistically analyzed using a mixed procedure of R. Opposite to what we had expected, neither of the 2 Fucus seaweeds reduced CH4 emissions from the dairy cows as daily CH4 production was significantly higher for both Fucus treatments compared with CON. Additionally, CH4 yield (g CH4/kg DMI) and intensity (g CH4/kg ECM) were significantly higher for SER compared with CON. Milk yield, DMI, and total-tract digestibility were unaffected by the treatments; however, SER resulted in lower milk protein yield (kg/d) and lower milk and blood plasma urea concentrations compared with CON. In conclusion, neither Fucus serratus (SER) nor Fucus vesiculosus (VES) showed potential as methane-mitigating feed additives when fed to dairy cows at an inclusion level of 4% of DM. The inclusion of the 2 brown seaweeds had no effects on DMI, milk yield, or total-tract digestibility.
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The aim of this work was to investigate the impact of the addition of salivary α-amylase on starch hydrolysis in protein-containing dispersions during an in vitro digestion process. In vitro digestion provides useful insights on the fate of nutrients during gastro-intestinal transit in complex food matrices, an important aspect to consider when developing highly nutritious foods. Many foods contain polysaccharides, and as their disruption in the gastric stage is limited, salivary α-amylase is often neglected in in vitro studies. A reference study on the effect of salivary α-amylase using one of the most advanced and complex in vitro digestion models (INFOGEST) is, however, not available. Hence, this work reports the gastrointestinal breakdown of three mixed dispersions containing whey protein isolate with different polysaccharides: potato starch, pectin from citrus peel and maize starch. The latter was also studied after heating. No polysaccharide or salivary α-amylase-dependent effect on protein digestion was found, based on the free NH2 and SDS-PAGE. However, in the heat-treated samples, the addition of salivary α-amylase showed a significantly higher starch hydrolysis compared to the sample without α-amylase, due to the gelatinization of the starch granules, which improved the accessibility of the starch molecules to the enzyme. This work demonstrated that the presence of different types of polysaccharides does not affect protein digestion, but also it emphasizes the importance of considering the influence of processing on food structure and its digestibility, even in the simplest model systems.
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Anthelmintic performance against equine cyathostomins can be evaluated by two different non-terminal measures; the Fecal Egg Count Reduction Test (FECRT) and the Egg Reappearance Period (ERP). Most available FECRT and ERP data have been determined in populations of young horses, and very little information is available from mature and senior horses. Furthermore, it is unknown how commonly occurring equine endocrine disorders such as Insulin dysregulation (ID) and Pituitary pars intermedia dysfunction (PPID) may interfere with these measurements, but it has been suggested that horses with these conditions could be more susceptible to parasitic infections. A research population of senior horses and horses with or without PPID, ID, or both were enrolled in this study. All strongylid egg count positive horses were included in an ivermectin (200⯵g/kg) efficacy study. These were distributed among the following groups: ID: six, PPID: three, PPID and ID: seven, and healthy controls: three. Strongylid fecal egg counts were determined on the day of ivermectin administration, at two weeks post deworming, and on weekly intervals until eight weeks post treatment. Determination of FECRT and ERP were carried out following World Association for the Advancement of Veterinary Parasitology guidelines. Results revealed high ivermectin efficacy with mean egg count reduction at 99.7% or above in all groups at two weeks post treatment. Egg reappearance was documented at six and seven weeks in the ID and PPID/ID groups, respectively, whereas the PPID and healthy control groups both had ERP at 8 weeks. Statistical analysis found no significant differences in egg count levels between groups during the study. The expected ERP for ivermectin is 8-10 weeks, meaning that two of the groups displayed shortened ERPs. However, due to the small group sizes, these data should be interpreted with caution. Nonetheless, results do indicate a need for further investigation of the possible influence of endocrine disorders on anthelmintic performance in horses.
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Fezes , Doenças dos Cavalos , Ivermectina , Contagem de Ovos de Parasitas , Animais , Cavalos , Ivermectina/uso terapêutico , Ivermectina/farmacologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/parasitologia , Contagem de Ovos de Parasitas/veterinária , Fezes/parasitologia , Feminino , Doenças do Sistema Endócrino/veterinária , Doenças do Sistema Endócrino/tratamento farmacológico , Masculino , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia , Antiparasitários/uso terapêutico , Antiparasitários/farmacologiaRESUMO
OBJECTIVE: Although remarkable strides have been made in fetal medicine and the prenatal diagnosis of congenital heart disease, around 60% of newborns with isolated coarctation of the aorta (CoA) are not identified prior to birth. The prenatal detection of CoA has been shown to have a notable impact on survival rates of affected infants. To this end, implementation of artificial intelligence (AI) in fetal ultrasound may represent a groundbreaking advance. We aimed to investigate whether the use of automated cardiac biometric measurements with AI during the 18-22-week anomaly scan would enhance the identification of fetuses that are at risk of developing CoA. METHODS: We developed an AI model capable of identifying standard cardiac planes and conducting automated cardiac biometric measurements. Our data consisted of pregnancy ultrasound image and outcome data spanning from 2008 to 2018 and collected from four distinct regions in Denmark. Cases with a postnatal diagnosis of CoA were paired with healthy controls in a ratio of 1:100 and matched for gestational age within 2 days. Cardiac biometrics obtained from the four-chamber and three-vessel views were included in a logistic regression-based prediction model. To assess its predictive capabilities, we assessed sensitivity and specificity on receiver-operating-characteristics (ROC) curves. RESULTS: At the 18-22-week scan, the right ventricle (RV) area and length, left ventricle (LV) diameter and the ratios of RV/LV areas and main pulmonary artery/ascending aorta diameters showed significant differences, with Z-scores above 0.7, when comparing subjects with a postnatal diagnosis of CoA (n = 73) and healthy controls (n = 7300). Using logistic regression and backward feature selection, our prediction model had an area under the ROC curve of 0.96 and a specificity of 88.9% at a sensitivity of 90.4%. CONCLUSIONS: The integration of AI technology with automated cardiac biometric measurements obtained during the 18-22-week anomaly scan has the potential to enhance substantially the performance of screening for fetal CoA and subsequently the detection rate of CoA. Future research should clarify how AI technology can be used to aid in the screening and detection of congenital heart anomalies to improve neonatal outcomes. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Coartação Aórtica , Inteligência Artificial , Coração Fetal , Ultrassonografia Pré-Natal , Humanos , Feminino , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/embriologia , Gravidez , Ultrassonografia Pré-Natal/métodos , Coração Fetal/diagnóstico por imagem , Coração Fetal/embriologia , Idade Gestacional , Biometria/métodos , Curva ROC , Sensibilidade e Especificidade , Dinamarca , Recém-Nascido , Adulto , Estudos de Casos e Controles , Valor Preditivo dos TestesRESUMO
INTRODUCTION: Complex interventional radiology procedures involve extensive fluoroscopy and image acquisition while staff are in-room. Monitoring occupational radiation dose is crucial in optimization. The purpose was to determine radiation doses received by staff involved in complex interventional procedures performed in a dedicated vascular or neuro intervention room. METHODS: Individual real-time radiation dose for all staff involved in vascular and neuro-interventional procedures in adult patients was recorded over a one-year period using wireless electronic dosimeters attached to the apron thyroid shield. A reference dosimeter was attached to the C-arm near the tube housing to measure scattered, unshielded radiation. Radiology staff carried shoulder thermo-luminescent dosimeters with monthly read-out to monitor dose over time. RESULTS: Occupational radiation dose was measured in 99 interventional procedures. In many cases prostate artery embolization procedures exposed radiologists to high radiation doses with a median of 15.0 µSv and a very large spread, i.e. 0.2-152.5 µSv. In all procedures except uterine fibroid embolization radiographers were exposed to lower doses than those of radiologists, with endovascular aortic repair being the procedure with highest median exposure to assisting radiographers, i.e. 2.2 µSv ranging from 0.1 to 36.1 µSv. Median radiation dose for the reference dosimeter was 670 µGy while median staff dose for all procedures combined was 3.2 µGy. CONCLUSION: Radiation doses for multiple staff were determined and the ratio between staff dose and reference dosimeter indicated proper use of shielding in general. Some high-dose procedures may need further optimization for certain staff members, especially those not primarily employed in radiology. IMPLICATIONS FOR PRACTICE: The study provides benchmark doses that may be used widely in audits and in the ongoing effort to optimize radiation protection for staff in interventional radiology.
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Proteção Radiológica , Masculino , Humanos , Doses de Radiação , FluoroscopiaRESUMO
Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients.
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Polipose Adenomatosa do Colo , Neoplasias Colorretais , Humanos , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Mutação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Desoxirribonuclease (Dímero de Pirimidina)/genéticaRESUMO
Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.
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Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Prótons , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Fótons/uso terapêutico , Probabilidade , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador , Dosagem RadioterapêuticaRESUMO
Animal-based agriculture and the production of protein-rich foods from animals, particularly from ruminants, are not sustainable and have serious climate effects. A new type of alternative proteins is now on the menu, namely animal proteins produced recombinantly by microbial fermentation. This new technology, precision fermentation, is projected to completely disrupt traditional animal-based agriculture. Certain milk and egg proteins along with specific meat substitute analog components produced by precision fermentation are already entering the market. This first wave of precision fermentation products targets the use of these proteins as protein additives, and several commercial players are already active in the field. The cost-efficiency requirements involve production titers above 50 g/L which are several orders of magnitude higher than those for pharmaceutical protein manufacture, making strain engineering, process optimization, and scale-up critical success factors. This new development within alternative proteins defines a new research direction integrating biotechnology, process engineering, and sustainable food protein production.
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Fermentação , Proteínas do Leite , Animais , Proteínas do Leite/metabolismo , Proteínas do Ovo/metabolismo , Proteínas Recombinantes , Tecnologia de Alimentos , Leite/química , Leite/microbiologiaRESUMO
Structural studies using x-ray scattering methods for investigating molecules in solution are shifting focus toward describing the role and effects of the surrounding solvent. However, forward models based on molecular dynamics (MD) simulations to simulate structure factors and x-ray scattering from interatomic distributions such as radial distribution functions (RDFs) face limitations imposed by simulations, particularly at low values of the scattering vector q. In this work, we show how the value of the structure factor at q = 0 calculated from RDFs sampled from finite MD simulations is effectively dependent on the size of the simulation cell. To eliminate this error, we derive a new scheme to renormalize the sampled RDFs based on a model of the excluded volume of the particle-pairs they were sampled from, to emulate sampling from an infinite system. We compare this new correction method to two previous RDF-correction methods, developed for Kirkwood-Buff theory applications. We present a quantitative test to assess the reliability of the simulated low-q scattering signal and show that our RDF-correction successfully recovers the correct q = 0 limit for neat water. We investigate the effect of MD-sampling time on the RDF-corrections, before advancing to a molecular example system, comprised of a transition metal complex solvated in a series of water cells with varying densities. We show that our correction recovers the correct q = 0 behavior for all densities. Furthermore, we employ a simple continuum scattering model to dissect the total scattering signal from the solvent-solvent structural correlations in a solute-solvent model system to find two distinct contributions: a non-local density-contribution from the finite, fixed cell size in NVT simulations, and a local contribution from the solvent shell. We show how the second contribution can be approximated without also including the finite-size contribution. Finally, we provide a "best-practices"-checklist for experimentalists planning to incorporate explicit solvation MD simulations in future work, offering guidance for improving the accuracy and reliability of structural studies using x-ray scattering methods in solution.
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Citrullination is an important post-translational modification (PTM) of arginine, known to play a role in autoimmune disorders, innate immunity response and maintenance of stem cell potency. However, citrullination remains poorly characterized and not as comprehensively understood compared to other PTMs, such as phosphorylation and ubiquitylation. High-resolution mass spectrometry (MS)-based proteomics offers a valuable approach for studying citrullination in an unbiased manner, allowing confident identification of citrullination modification sites and distinction from deamidation events on asparagine and glutamine. MS efforts have already provided valuable insights into peptidyl arginine deaminase targeting along with site-specific information of citrullination in for example synovial fluids derived from rheumatoid arthritis patients. Still, there is unrealized potential for the wider citrullination field by applying MS-based mass spectrometry approaches for proteome-wide investigations. Here we will outline contemporary methods and current challenges for studying citrullination by MS, and discuss how the development of neoteric citrullination-specific proteomics approaches still may improve our understanding of citrullination networks. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.
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Citrulinação , Espectrometria de Massas , Proteômica , Humanos , Arginina , Processamento de Proteína Pós-Traducional , Proteoma , Proteômica/métodosRESUMO
BACKGROUND: People with a severe mental illness (SMI) have shorter life expectancy and poorer quality of life compared to the general population. Most years lost are due to cardiovascular disease, respiratory disease, and various types of cancer. We co-designed an intervention to mitigate this health problem with key stakeholders in the area, which centred on an extended consultations for people with SMI in general practice. This study aimed to1) investigate general practitioners' (GPs) experience of the feasibility of introducing extended consultations for patients with SMI, 2) assess the clinical content of extended consultations and how these were experienced by patients, and 3) investigate the feasibility of identification, eligibility screening, and recruitment of patients with SMI. METHODS: The study was a one-armed feasibility study. We planned that seven general practices in northern Denmark would introduce extended consultations with their patients with SMI for 6 months. Patients with SMI were identified using practice medical records and screened for eligibility by the patients' GP. Data were collected using case report forms filled out by practice personnel and via qualitative methods, including observations of consultations, individual semi-structured interviews, a focus group with GPs, and informal conversations with patients and general practice staff. RESULTS: Five general practices employing seven GPs participated in the study, which was terminated 3 ½ month ahead of schedule due to the COVID-19 pandemic. General practices attempted to contact 57 patients with SMI. Of these, 38 patients (67%) attended an extended consultation, which led to changes in the somatic health care plan for 82% of patients. Conduct of the extended consultations varied between GPs and diverged from the intended conduct. Nonetheless, GPs found the extended consultations feasible and, in most cases, beneficial for the patient group. In interviews, most patients recounted the extended consultation as beneficial. DISCUSSION: Our findings suggest that it is feasible to introduce extended consultations for patients with SMI in general practice, which were also found to be well-suited for eliciting patients' values and preferences. Larger studies with a longer follow-up period could help to assess the long-term effects and the best implementation strategies of these consultations.
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COVID-19 , Medicina Geral , Transtornos Mentais , Humanos , Estudos de Viabilidade , Pandemias , Qualidade de Vida , COVID-19/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Encaminhamento e ConsultaRESUMO
Reduction in enteric methane (CH4) emissions from cattle can be achieved through use of feed additives, which often results in increased emission of hydrogen (H2). The objective of this study was to investigate in vitro effects of a known hydrogen sink, fumaric acid, in combination with either of 2 methane inhibitors, the macroalga Asparagopsis taxiformis or nitrate, on CH4 and H2 production, feed degradability, pH, and redox potential. A corn silage (0.5 g; control) was incubated in buffered rumen fluid with the addition of 0.025 g of nitrate (Nit), 0.025 g of dried A. taxiformis (Asp), 0.025 g of nitrate + 0.025 g of fumaric acid (Nit+Fum), or 0.025 g of dried A. taxiformis + 0.025 g of fumaric acid (Asp+Fum). Accumulated gas production was determined using the AnkomRF system equipped with airtight gasbags. There were 9 replicates per treatment with 3 replicates per treatment stopped after 24, 36, and 48 h of incubation. The amount of undegraded feed was determined by filtration. Gas composition was determined by gas chromatography. Degradable dry matter, degradable organic matter, pH, redox potential, and gas production data were analyzed using a mixed model. Asp and Asp+Fum reduced CH4 production by 98% or greater at all incubation times, whereas Nit and Nit+Fum reduced CH4 production (mL of CH4/g of dry matter) by 52% to 63% compared with the control. Hydrogen was only detectable in gas from Asp and Asp+Fum treatments, with no difference in H2 production between the 2 treatments. The treatments had only minor effects on redox potential in the fermented rumen fluid, and pH was lowest for treatments including A. taxiformis. In conclusion, both A. taxiformis and nitrate reduced CH4 production. Fumaric acid in combination with A. taxiformis did not reduce H2 production, and treatments including nitrate did not result in any detectable levels of H2. Future dose-response in vitro studies will contribute to investigating the potential of fumaric acid as a hydrogen sink during CH4 mitigation.
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Macroalgae are receiving increased attention as antimethanogenic feed additives for cattle, but most in vivo studies are limited to investigating effects of the red macroalgae Asparagopsis spp. Hence, this study aimed to investigate the CH4 mitigating potential of 3 brown macroalgae from the Northern Hemisphere when fed to dairy cows, and to study the effects on feed intake, milk production, feed digestibility, and animal health indicators. The experiment was conducted as a 4 × 4 Latin square design using 4 lactating rumen, duodenal, and ileal cannulated Danish Holstein dairy cows. The cows were fed a total mixed ration (TMR) without any macroalgae or the same TMR diluted with, on a dry matter basis, either 4% ensiled Saccharina latissima, 4% Ascophyllum nodosum (NOD), or 2% Sargassum muticum (MUT). Each period consisted of 14 d of adaptation, 3 d of digesta and blood sampling, and 4 d of gas exchange measurements using respiration chambers. Milk yield and dry matter intake (DMI) were recorded daily. Blood was sampled on d 13 and 16 and analyzed for health status indicators. None of the 3 species affected the CH4 emission. Moreover, milk yield and DMI were also unaffected. Total-tract digestibility of crude protein was significantly lower for NOD compared with other diets, and additionally, the NOD diet also tended to reduce total-tract digestibility of neutral detergent fiber compared with MUT. Blood biomarkers did not indicate negative effects of the dietary inclusion of macroalgae on cow health. In conclusion, none of the 3 brown macroalgae reduced CH4 emission and did not affect DMI and milk production of dairy cows, whereas negative effects on the digestibility of nutrients were observed when A. nodosum was added. None of the diets would be allowed to be fed in commercial dairy herds due to high contents of iodine, cadmium, and arsenic.
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Alga Marinha , Feminino , Bovinos , Animais , Lactação , Dieta/veterinária , Duodeno , MetanoRESUMO
Anoplocephalid tapeworms are commonly occurring in grazing horses around the world. Two currently available anthelmintics have documented high efficacy against Anoplocephala perfoliata; praziquantel in various dosages ranging from 1.0 to 2.5 mg/kg and pyrantel pamoate administered at 13.2 mg base/kg. Anthelmintic resistance has not been reported in A. perfoliata, but anecdotal reports made during 2022 have suggested a possible loss of efficacy for both actives. This paper reports fecal egg count data from a Thoroughbred operation in Central Kentucky in 2023. Fifty-six yearlings were first dewormed with a combination of ivermectin (200 µg/kg) and praziquantel (1.5 mg/kg) and subsequently treated with pyrantel pamoate (13.2 mg base/kg). Fecal egg counts were determined at the day of treatment and again 14 days post-treatment. Two groups of mares (n = 39 and 45) were also treated with ivermectin/praziquantel and examined pre- and post-treatment. Low efficacy of ivermectin and pyrantel pamoate was demonstrated against strongylid parasites in the yearlings with mean Fecal Egg Count Reductions (FECRs) at 75.6% or below and upper 95% credible interval (CI) limits below 90% in all cases. Overall anti-cestodal FECR levels in the yearlings were 23.5% (95% CI: 11.2-48.0) for praziquantel and 50.9% (20.5-72.0) for pyrantel pamoate. Praziquantel eliminated anoplocephalid eggs from three of 17 yearlings, but another 5 yearlings went from negative to positive status following treatment. Pyrantel pamoate failed to eliminate anoplocephalid eggs from any of 14 treated tapeworm-positive yearlings. Nine of 84 mares tested positive for anoplocephalid eggs, and seven of these were still positive post praziquantel treatment. These findings sharply contrast data from historic field efficacy studies conducted for both actives and raise concern about anthelmintic resistance having possibly developed. This emphasizes the need for developing and refining antemortem methodologies for evaluating anti-cestodal treatment efficacy and for searching for possible alternative treatment options.
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Anti-Helmínticos , Cestoides , Doenças dos Cavalos , Animais , Cavalos , Feminino , Pamoato de Pirantel/uso terapêutico , Praziquantel/uso terapêutico , Ivermectina/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/parasitologia , Anti-Helmínticos/uso terapêutico , Falha de Tratamento , Fezes/parasitologia , Resultado do Tratamento , Contagem de Ovos de Parasitas/veterináriaRESUMO
RATIONALE: Dopaminergic dysfunction is implicated in disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) has been used to quantify changes in attention and impulsivity. OBJECTIVE: To examine the roles of dopamine receptors in attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval schedules (vITI) using DA receptor antagonists. METHODS: Two cohorts of 35 and 36 female C57BL/6JRj mice were examined separately in the rCPT, vSD, and vITI schedules, respectively. Both cohorts received antagonists of the following receptors: D1/5 (SCH23390, SCH: 0.01, 0.02, 0.04 mg/kg) and D2/3 (raclopride, RAC 0.03, 0.10, 0.30 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity. RESULTS: SCH showed similar effects in both schedules, and the effects were reference-dependent in the vITI schedule. SCH reduced responding, but improved response accuracy, impulsivity, discriminability, and locomotor activity. RAC showed mixed effects on responsivity, but improved accuracy and discriminability. The discriminability improvement was driven by an increase in hit rate in the vITI schedule and a reduction in false alarm rate in the vSD schedule. RAC also decreased locomotor activity. CONCLUSION: Both D1/5 and D2/3 receptor antagonism reduced responding, but the outcome on discriminability differed, stemming from individual effects on hit and false alarm rate, and the weight of omissions within the calculation. The effects of SCH and RAC suggest that endogenous DA increases responding and impulsivity, but reduces accuracy and shows mixed effects on discriminability.
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Antagonistas de Dopamina , Roedores , Camundongos , Animais , Feminino , Antagonistas de Dopamina/farmacologia , Camundongos Endogâmicos C57BL , Receptores de Dopamina D1 , Atenção , Comportamento Impulsivo , Antagonistas dos Receptores de Dopamina D2/farmacologia , Benzazepinas/farmacologia , Relação Dose-Resposta a DrogaRESUMO
RATIONALE: Noradrenergic dysfunction is associated with disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) quantifies changes in attention and impulsivity. OBJECTIVE: To use NA receptor antagonists to examine the roles of NA on attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval (vITI) schedules. METHODS: Two cohorts of 36 female C57BL/6JRj mice were examined separately in the rCPT vSD and vITI schedules. Both cohorts received antagonists of the following adrenoceptors: α1 (doxazosin, DOX: 1.0, 3.0, 10.0 mg/kg), α2 (yohimbine, YOH: 0.1, 0.3, 1.0 mg/kg), and ß1/2 (propranolol, PRO: 1.0, 3.0, 10.0 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity. RESULTS: DOX showed similar effects in both schedules, improving discriminability and accuracy, and reducing responding and impulsivity, and DOX also reduced locomotor activity. YOH showed prominent effects in the vSD schedule to increase responding and impulsivity, while impairing discriminability and accuracy. YOH did not affect locomotor activity. PRO increased responding and impulsivity, decreased accuracy, but did not affect discriminability or locomotor activity. CONCLUSION: Antagonism of α2 or ß1/2 adrenoceptors caused similar increases in responding and impulsivity and worsened attentional performance, while α1 adrenoceptor antagonism showed the opposite effects. Our results suggest that endogenous NA exerts bidirectional control of most behaviours in the rCPT. The parallel vSD and vITI studies showed a substantial overlap in effects, but also some differences that indicate differing sensitivity towards noradrenergic manipulations.
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Norepinefrina , Roedores , Camundongos , Animais , Feminino , Norepinefrina/farmacologia , Camundongos Endogâmicos C57BL , Atenção , Comportamento Impulsivo/fisiologia , Receptores AdrenérgicosRESUMO
Concerns have been raised about the predictability of achieving appropriate tibial plateau angles (TPA), the occurrence of axis shift and tibial length reduction following cranial closing wedge ostectomy (CCWO). The primary objective of this review was to quantify typical errors in achieving target TPA with CCWO, with secondary objectives of assessing axis shift and length reduction. Retrospective or prospective studies of CCWO used as the primary treatment, from any date and in English, were eligible for inclusion. Searches were performed in EMBASE, Ovid MEDLINE, Agricola, Scopus, Web of Science, and CAB abstracts. Risk of bias was assessed, and data were screened for outliers and influential cases. Extracted data from 11 included studies were tabulated and underwent meta-analysis using R. Mean errors in TPA after CCWO ranged from - 0.6-2.9°, indicating the possibility of both under- and over-correction depending on the selected technique. Errors were relatively consistent for technique subgroups. Mean axis shifts ranged from 3.4° to 5.2°, and length reduction ranged from 0.4% to 3.2% of initial length, based on 6/11 and 3/11 studies, respectively. Data had high heterogeneity, many studies had small populations, and reporting standards were inconsistent. Concerns about the predictability of postoperative TPA may be overstated. With the limited data available, limb shortening does not appear to be a clinically important consideration. Axis shift will occur to varying degrees and must be considered during CCWO planning, as it influences the postoperative TPA. Careful choice of CCWO technique may allow clinicians to reliably achieve predictable TPA values.
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Lesões do Ligamento Cruzado Anterior , Doenças do Cão , Animais , Cães , Ligamento Cruzado Anterior/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Osteotomia/métodos , Osteotomia/veterinária , Tíbia/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/veterinária , Joelho de Quadrúpedes , Doenças do Cão/cirurgiaRESUMO
BACKGROUND: Hop performance evaluation in children after anterior cruciate ligament (ACL) reconstruction may benefit from comparison to healthy controls. Thus, the purpose was to investigate the hop performance in children one year after ACL reconstruction with a comparison to healthy controls. METHODS: Hop performance data from children with ACL reconstruction one year post-surgery and healthy children were compared. Four one-legged hop test data were analyzed: 1) single hop (SH), 2) 6 m timed hop (6 m-timed), 3) triple hop (TH), and 4) cross-over hop (COH). Outcomes were the best result (longest/fastest hop) from each leg and limb asymmetry. Differences in hop performance between-limbs (operated versus non-operated) and between-groups were estimated. RESULTS: 98 children with ACL reconstruction and 290 healthy children were included. Few statistically significant group differences were observed. Girls with ACL reconstruction outperformed healthy controls in two tests on the operated leg SH, COH) and in three tests on the non-operated leg (SH, TH, COH). However, the girls performed 4-5% worse on the operated leg when compared to the non-operated leg in all hop tests. No statistically significant between-group differences in the limb asymmetry were found. CONCLUSION: The hop performance in children with ACL reconstruction one year post-surgery was largely comparable to the level of healthy controls. Despite this, we cannot exclude that neuromuscular deficits exist among the children with ACL reconstruction. The inclusion of a healthy control group for evaluating hop performance evoked complex findings regarding the ACL reconstructed girls. Thus, they may represent a selected group.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Feminino , Humanos , Criança , Lesões do Ligamento Cruzado Anterior/cirurgia , Estudos Transversais , Nível de SaúdeRESUMO
With raising consumer demand for plant-derived proteins, there has been an increased interest in the utilization of pea ingredients in food formulations. It was hypothesized that differences in processing history and composition affect their colloidal properties and their breakdown during in vitro simulated gastrointestinal digestion. The gastrointestinal fate of three different commercial pea protein ingredients, two protein isolates and one less refined concentrate was compared. The concentrate dispersion showed greater solubility, different protein composition and smaller particle size than the reconstituted pea protein isolates. When heat-treated, the release of free amino groups decreased for the isolates, but increased for the concentrate dispersions. LC-TQMS of free amino acids in the intestinal digestates indicated a significantly higher release of methionine (limiting amino acid in pea protein) in the concentrates than in the isolates. This work highlights the influence of processing and composition on techno-functional and digestion properties of pea ingredients.
Assuntos
Proteínas de Ervilha , Pós , Aminoácidos/metabolismo , Proteínas de Plantas/metabolismo , MetioninaRESUMO
OBJECTIVE: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. METHOD: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. RESULTS: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1ß and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). CONCLUSIONS: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.