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1.
Artif Life ; : 1-23, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656414

RESUMO

The field of Artificial Life studies the nature of the living state by modeling and synthesizing living systems. Such systems, under certain conditions, may come to deserve moral consideration similar to that given to nonhuman vertebrates or even human beings. The fact that these systems are nonhuman and evolve in a potentially radically different substrate should not be seen as an insurmountable obstacle to their potentially having rights, if they are sufficiently sophisticated in other respects. Nor should the fact that they owe their existence to us be seen as reducing their status as targets of moral concern. On the contrary, creators of Artificial Life may have special obligations to their creations, resembling those of an owner to their pet or a parent to their child. For a field that aims to create artificial life-forms with increasing levels of sophistication, it is crucial to consider the possible ethical implications of our activities, with an eye toward assessing potential moral obligations for which we should be prepared. If Artificial Life is larger than life, then the ethics of artificial beings should be larger than human ethics.

2.
Nanomedicine (Lond) ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661720

RESUMO

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.

3.
J Am Vet Med Assoc ; : 1-8, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663440

RESUMO

Antimicrobial use (AMU) contributes to the emergence of antimicrobial resistance, necessitating antimicrobial stewardship actions across all sectors using a One Health approach to preserve antimicrobial effectiveness. This overview delves into 2 FDA-funded projects focused on collecting and analyzing AMU data in major food-producing animal species (cattle, swine, turkeys, and chickens). Initiated in 2016, the projects aimed to establish baseline AMU information and pilot methodologies. This article describes the methodologies used by grantees for data collected from 2016 to 2021, emphasizing the diverse data sources and metrics utilized. Instead of summarizing the trends, it provides a list of publications generated from the grants. Factors contributing to successful data collection included early interaction and trust building between the producers/data holders and researchers. Shared challenges include limitations stemming from convenience sampling, variable industry participation, and lack of data covering all segments of a particular commodity (eg, data on breeding or young animals were lacking). Future collaborative efforts are needed to enhance data standardization, contextualization, representativeness, and reporting of national-scale AMU data going forward. Addressing these challenges and data gaps is essential for effective monitoring of AMU in veterinary settings and animal agriculture, in alignment with national strategies to combat antimicrobial resistance.

4.
Sci Rep ; 14(1): 9546, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664496

RESUMO

The aim of the current study was to investigate the influence of both intra- and interspecific audiences on dogs' facial expressions and behaviours. Forty-six dogs were exposed to three test conditions in which a food reward, initially available, was denied when in the presence of either a human (Human condition) or a dog audience (Dog condition), or in the absence of a visible audience (Non-social condition). Salivary cortisol was collected to evaluate the stress/arousal activation in the different conditions. Compared to the Non-social condition, the presence of a conspecific evoked more facial expressions, according to the DogFACS (Facial Action Coding System, an anatomically based tool to analyze facial expressions in domestic dogs), (EAD105-Ears downward), displacement behaviours (AD137-Nose licking, AD37-Lip wiping), tail wagging, whining, and panting (AD126). When facing a conspecific, dogs assumed a more avoidant attitude, keeping a distance and not looking at the stimuli, compared to when in the presence of the human partner. Dogs also exhibited more facial expressions (EAD102-Ears Adductor, EAD104-Ears Rotator), displacement behaviours (AD137-Nose licking, AD37-Lip wiping), panting (AD126) and whining when facing the conspecific than the human partner. Post-test cortisol was not influenced by any condition, and no association between pre-test cortisol and behavioural variables was found, thus strong differences in the levels of stress/arousal were unlikely to be responsible for differences in behavior between conditions. Considering the current results in the context of the available literature, we suggest that the higher displacement behaviors exhibited with the conspecifics were likely due to an increased level of uncertainty regarding the situations.


Assuntos
Comportamento Animal , Expressão Facial , Hidrocortisona , Animais , Cães , Comportamento Animal/fisiologia , Masculino , Hidrocortisona/metabolismo , Hidrocortisona/análise , Feminino , Humanos , Saliva/metabolismo , Saliva/química , Estresse Psicológico , Comportamento Social
5.
Heliyon ; 10(7): e28421, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623251

RESUMO

This behavioral study was undertaken to provide empirical evidence in favor of or opposed to the notion that animals across a wide breadth of the animal kingdom have subjective (personal) experience that varies with their lifestyles, ecological constraints, or phylogeny. Twelve species representing two invertebrate phyla and six vertebrate classes were observed unobtrusively in 15-min episodes, during which three modes of behavior (volitional, interactive, and egocentric) were quantified according to the frequency, variety, and dynamism of each mode. Volitional behavior was the most prevalent and dynamic mode for nearly all species, largely without regard to phylogenetic position. Interactive behavior likewise varied inconsistently across the entire evolutionary spectrum. Egocentric behavior was concentrated among the avian and mammalian species, but evidence of it were observed in the invertebrate species as well. Diagrams of the matrix constructed from the three qualitative modes and three quantitative attributes for each mode provide a metaphorical representation of the unique experiential profile of each species. To the extent that these behavioral measures correlate with the nature of the animal's subjective experience, they support the growing view that phenomenology is heterogeneous, multimodal, and non-linear in extent across the animal kingdom.

6.
Gastroenterol Rep (Oxf) ; 12: goae021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634007

RESUMO

Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice are frequently employed due to their practicality and genetic manipulability. However, for studies aiming to closely mimic human pathology, non-human primates such as monkeys and dogs offer valuable physiological parallels. Guinea pigs, while less commonly used, present unique advantages for investigating the intricate interplay between neurological and immunological factors in IBD. Additionally, New Zealand rabbits excel in endoscopic biopsy techniques, providing insights into mucosal inflammation and healing processes. Pigs, with their physiological similarities to humans, serve as ideal models for exploring the complex relationships between nutrition, metabolism, and immunity in IBD. Beyond mammals, non-mammalian organisms including zebrafish, Drosophila melanogaster, and nematodes offer specialized insights into specific aspects of IBD pathology, highlighting the diverse array of model systems available for advancing our understanding of this multifaceted disease. In this review, we conduct a thorough analysis of various animal models employed in IBD research, detailing their applications and essential experimental parameters. These include clinical observation, Disease Activity Index score, pathological assessment, intestinal barrier integrity, fibrosis, inflammatory markers, intestinal microbiome, and other critical parameters that are crucial for evaluating modeling success and drug efficacy in experimental mammalian studies. Overall, this review will serve as a valuable resource for researchers in the field of IBD, offering insights into the diverse array of animal models available and their respective applications in studying IBD.

7.
J Orthop ; 55: 23-31, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38638113

RESUMO

This systematic review, registered with Prospero, aims to identify an optimal animal model for meniscus repair research, moving from ex vivo experimentation to in vivo studies. Data sources included PubMed, Medline, all Evidence-Based Medicine Reviews, Web of Science, and Embase searched in March 2023. Studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data including animal model, type of experiment, type of tear, surgical techniques, and measured outcomes, were recorded, reviewed, and analyzed by four independent reviewers. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) Rob tool was used for critical appraisal and risk of bias assessment. Out of 11,719 studies, 72 manuscripts were included for data extraction and analysis; 41 ex vivo extra-articular studies, 20 ex vivo intra-articular studies, and only 11 in vivo studies. Six animal models were employed: porcine, bovine, lapine, caprine, canine, and ovine. Longitudinal lesions were the most frequently studied tear pattern and sutures the most common repair technique. Studied outcomes focused mainly on biomechanical assessments and gross observations. This systematic review can guide researchers in their choice of animal model for meniscus repair research; it highlighted the strengths of the porcine, caprine, and bovine models for ex vivo cadaveric studies, while the porcine and caprine models were found to be more suited to in vivo studies due to their similarities with human anatomy. Research teams should familiarize themselves with the advantages and disadvantages of various animal models before initiating protocols to improve standardization in the field.

8.
Orthopadie (Heidelb) ; 53(5): 336-340, 2024 May.
Artigo em Alemão | MEDLINE | ID: mdl-38578461

RESUMO

Due to the legal implantation of the 3R principle, the number of laboratory animals decreased significantly over the past 10 years. In this article, the historical development of animal experiments over the last decade will be presented in the context of the current regulations of the Animal Welfare Act. It points out bureaucratic obstacles to the approval of animal experiments, which jeopardize Germany as a research location for both academia and industry. The article presents constructive proposals for solutions. This should be done in accordance with the DFG recommendation to ensure efficient biomedical research while maintaining the highest animal welfare standards.


Assuntos
Experimentação Animal , Bem-Estar do Animal , Bem-Estar do Animal/legislação & jurisprudência , Bem-Estar do Animal/ética , Experimentação Animal/legislação & jurisprudência , Experimentação Animal/ética , Animais , Alemanha , Pesquisa Biomédica/legislação & jurisprudência
9.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38581277

RESUMO

Accelerometers are useful in analyzing lying behavior in farm animals. The effect of the farrowing system on sow lying behavior has been studied around parturition, but not long-term. In a natural environment, sows increase activity 14 d post parturition, which we expected to be also evident in housed sows when they can move freely. The objective of this study was (1) to validate the methodology to automatically measure sow lying bouts and duration with accelerometers and (2) to apply it to crated and free-farrowing sows 24-h pre-parturition until weaning. We used videos with manual behavior coding as the gold standard for validation and calculated the agreement with an intraclass correlation coefficient (ICC), which was 0.30 (95% CI: -0.10 to 0.64) for the number of lying bouts. When transitional sitting bouts were excluded from the video dataset, the ICC for lying bouts increased to 0.86 (95% CI: 0.40 to 0.95). For lying duration, the ICC was 0.93 (95% CI: 0.26 to 0.98). We evaluated the effects of housing, day relative to parturition, and time of day on lying using the accelerometer data and linear mixed models. In crated sows, the number of lying bouts increased toward parturition, peaking at about five bouts per 6 h, and decreased to almost zero bouts after parturition. Then, it increased again (P = 0.001). In free-farrowing sows, the number of lying bouts gradually decreased from a high level towards parturition and was lowest after parturition. It remained constant, as in the crated sows, until day 15, when the number of bouts increased to eight bouts on day 20 (P = 0.001). Sows in both systems were lying almost all of the time between 18:00 and 00:00 hours and on all days (P = 0.001). The crated sows showed a very similar pattern in the other three-quarters of the day with a reduced lying time before parturition, a peak after parturition, reduced lying time from days 5 to 20, and an increase again towards weaning (P = 0.001). Free-farrowing sows had a similar pattern to the crated sows from 00:00 to 06:00 hours, but without the reduction in lying time from days 5 to 20. They showed an increase in lying time toward parturition, which remained constant with a final decrease toward weaning, especially during the day (P = 0.001). This study proves the accuracy of accelerometer-based sow lying behavior classification and shows that free-farrowing systems benefit lactating sows around parturition but also towards weaning in the nest-leaving phase by facilitating activity.


We analyzed lying behavior of sows using sensors, focusing on crated versus free-farrowing sows from pre-parturition to weaning. Lying behavior varies in this time following the needs of the sow and her litter. In a natural environment, sows increase activity 14 d post parturition, which we expected to be also evident in housed sows when they are allowed to move freely. Validation with video data showed excellent agreement for duration and frequency of lying. In crated sows, the number of lying bouts peaked around parturition, decreased after parturition, and then gradually increased. In free-farrowing sows, lying down occurred less often before parturition, but increased by day 20 compared to crated sows. Both housing systems showed prolonged lying periods from 18:00 to 00:00 hours. Crated sows had reduced lying times before parturition and lied longest post-parturition, which decreased until day 5 and then increased toward weaning. Free-farrowing sows had similar nocturnal patterns but persistent lying times that increased prior to parturition and decreased prior to weaning. Overall, the study highlighted the accuracy of accelerometer-based lying behavior classification and showed that free-farrowing systems benefit lactating sows not only around parturition but also toward weaning, facilitating activity during the nest-leaving phase.


Assuntos
Acelerometria , Comportamento Animal , Abrigo para Animais , Animais , Feminino , Acelerometria/veterinária , Acelerometria/instrumentação , Suínos/fisiologia , Parto/fisiologia , Gravidez , Criação de Animais Domésticos/métodos
10.
Am J Clin Nutr ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599522

RESUMO

BACKGROUND: With the growing popularity of plant-based meat analogs (PBMAs), an investigation of their effects on health is warranted in Asian population. OBJECTIVES: This research investigated the impact of consuming an omnivorous animal-based meat diet (ABMD) compared with a PBMAs diet (PBMD) on cardiometabolic health among adults with elevated risk of diabetes in Singapore. METHODS: In an 8-wk parallel design randomized controlled trial, participants (n = 89) were instructed to substitute habitual protein-rich foods with fixed quantities of either PBMAs (n = 44) or their corresponding animal-based meats (n = 45; 2.5 servings/d), maintaining intake of other dietary components. Low-density lipoprotein cholesterol served as primary outcome, whereas secondary outcomes included other cardiometabolic disease-related risk factors (e.g. glucose and fructosamine), dietary data, and within a subpopulation, ambulatory blood pressure measurements (n = 40) at baseline and postintervention, as well as a 14-d continuous glucose monitor (glucose homeostasis-related outcomes; n = 37). RESULTS: Data from 82 participants (ABMD: 42 and PBMD: 40) were examined. Using linear mixed-effects model, there were significant interaction (time × treatment) effects for dietary trans-fat (increased in ABMD), dietary fiber, sodium, and potassium (all increased in PBMD; P-interaction <0.001). There were no significant effects on the lipoprotein profile, including LDL cholesterol. Diastolic blood pressure (DBP) was lower in the PBMD group (P-interaction=0.041), although the nocturnal DBP markedly increased in ABMD (+3.2% mean) and was reduced in PBMD (-2.6%; P-interaction =0.017). Fructosamine (P time=0.035) and homeostatic model assessment for ß-cell function were improved at week 8 (P time=0.006) in both groups. Glycemic homeostasis was better regulated in the ABMD than PBMD groups as evidenced by interstitial glucose time in range (ABMD median: 94.1% (Q1:87.2%, Q3:96.7%); PBMD: 86.5% (81.7%, 89.4%); P = 0.041). The intervention had no significant effect on the other outcomes examined. CONCLUSIONS: A PBMA diet did not show widespread cardiometabolic health benefits compared with omnivorous diets <8 wk. The composition of PBMAs may need to be considered in future trials. This trial was registered at https://clinicaltrials.gov/as NCT05446753.

11.
Braz J Anesthesiol ; 74(3): 844502, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604407

RESUMO

BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

12.
Zebrafish ; 21(2): 73-79, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38621202

RESUMO

The goal of the University of Wisconsin-Milwaukee WInSTEP SEPA program is to provide valuable and relevant research experiences to students and instructors in diverse secondary educational settings. Introducing an online experience allows the expansion of a proven instructional research program to a national scale and removes many common barriers. These can include lack of access to zebrafish embryos, laboratory equipment, and modern classroom facilities, which often deny disadvantaged and underrepresented students from urban and rural school districts valuable inquiry-based learning opportunities. An online repository of zebrafish embryo imagery was developed in the Carvan laboratory to assess the effects of environmental chemicals. The WInSTEP SEPA program expanded its use as an accessible online tool, complementing the existing classroom experience of our zebrafish module. This virtual laboratory environment contains images of zebrafish embryos grown in the presence of environmental toxicants (ethanol, caffeine, and nicotine), allowing students to collect data on 19 anatomical endpoints and generate significant amounts of data related to developmental toxicology and environmental health. This virtual laboratory offers students and instructors the choice of data sets that differ in the independent variables of chemical concentration and duration of postfertilization exposure. This enables students considerable flexibility in establishing their own experimental design to match the curriculum needs of each instructor.


Assuntos
Estudantes , Peixe-Zebra , Animais , Humanos , Saúde Ambiental/educação , Aprendizagem , Laboratórios , Currículo
13.
MAbs ; 16(1): 2343499, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634488

RESUMO

There is no doubt that today's life sciences would look very different without the availability of millions of research antibody products. Nevertheless, the use of antibody reagents that are poorly characterized has led to the publication of false or misleading results. The use of laboratory animals to produce research antibodies has also been criticized. Surprisingly, both problems can be addressed with the same technology. This review charts today's maze of different antibody formats and the various methods for antibody production and their interconnections, ultimately concluding that sequence-defined recombinant antibodies offer a clear path to both improved quality of experimental data and reduced use of animals.


Assuntos
Anticorpos , Biblioteca de Peptídeos , Animais , Anticorpos/genética , Proteínas Recombinantes
14.
Mov Ecol ; 12(1): 31, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654348

RESUMO

BACKGROUND: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. METHODS: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. RESULTS: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array. CONCLUSION: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

15.
Front Med (Lausanne) ; 11: 1276420, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654839

RESUMO

Drug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable in vivo models are warranted in new imaging biomarker development to accelerate better-targeted treatment options. Single-dose bleomycin models have, for a long time, served as a reference model in fibrosis and lung injury research. Here, we aimed to use a clinically more relevant animal model by systemic exposure to bleomycin and assessing disease progression over time by combined magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging. Methods: C57BL/6 mice received bleomycin (i.p. 35iU/kg) or saline as control twice per week for 4 weeks. Mice were monitored until 2 weeks after cessation of bleomycin administration (w4 + 1 and w4 + 2), referred to as the resting period. MRI scans were performed in weeks 3 and 4 and during the resting weeks. [18F]FDG-PET was performed at the last week of dosing (w4) and 2 weeks after the last dosing (w4 + 2). Lung tissue sections were stained with Masson's trichrome and evaluated by modified Ashcroft scoring. Lung volume and lesion volumes were assessed using MRI, as well as 3D mapping of the central airways. Results and discussion: Bleomycin-challenged mice showed increased lung weights (p < 0.05), while total lung volume was unchanged (w4 and onward). Histology analysis demonstrated fibrotic lesions emanating from the distal parts of the lung. Fibrosis progression was visualized by MRI with significantly increased high signal in bleomycin-exposed lungs compared to controls (p < 0.05). In addition, a significant increase in central airway diameter (p < 0.01) was displayed in bleomycin-exposed animals compared to controls and further continued to dilate as the disease progressed, comparing the bleomycin groups over time (p < 0.05-0.001). Lung [18F]FDG uptake was significantly elevated in bleomycin-exposed mice compared to controls (p < 0.05). Conclusion: Non-invasive imaging displayed progressing lesions in the lungs of bleomycin-exposed mice, using two distinct MRI sequences and [18F]FDG-PET. With observed fibrosis progression emanating from distal lung areas, dilation of the central airways was evident. Taken together, this chronic bleomycin-exposure model is translationally more relevant for studying lung injury in ILD and particularly in the context of DIILD.

16.
Front Pharmacol ; 15: 1369489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655187

RESUMO

Introduction: Pulmonary arterial hypertension (PAH) is characterised by endothelial dysfunction and pathological vascular remodelling, resulting in the occlusion of pulmonary arteries and arterioles, right ventricular hypertrophy, and eventually fatal heart failure. Targeting the apelin receptor with the novel, G protein-biased peptide agonist, MM07, is hypothesised to reverse the developed symptoms of elevated right ventricular systolic pressure and right ventricular hypertrophy. Here, the effects of MM07 were compared with the clinical standard-of-care endothelin receptor antagonist macitentan. Methods: Male Sprague-Dawley rats were randomised and treated with either normoxia/saline, or Sugen/hypoxia (SuHx) to induce an established model of PAH, before subsequent treatment with either saline, macitentan (30 mg/kg), or MM07 (10 mg/kg). Rats were then anaesthetised and catheterised for haemodynamic measurements, and tissues collected for histopathological assessment. Results: The SuHx/saline group presented with significant increases in right ventricular hypertrophy, right ventricular systolic pressure, and muscularization of pulmonary arteries compared to normoxic/saline controls. Critically, MM07 was as at least as effective as macitentan in significantly reversing detrimental structural and haemodynamic changes after 4 weeks of treatment. Discussion: These results support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.

17.
Sci Rep ; 14(1): 9447, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658774

RESUMO

Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups. Group A was given a normal formula diet for 13 weeks. Group C underwent surgery on the intima of the right carotid artery with - 80 °C cryofluid-induced injury after 1 week of a high-fat diet and further feeding a 12-week high-fat diet. Group B underwent the same procedure as Group C but without the - 80 °C cryofluid. Serum lipid levels were detected via ELISA. The plaque morphology, stability and degree of stenosis were evaluated through hematoxylin-eosin (HE) staining, Masson trichrome staining, Elastica van Gieson staining (EVG), and oil red O staining. Macrophages and inflammatory factors in the plaques were assessed via immunohistochemical analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels in groups B and C were significantly greater than those in group A. No plaque formation was observed in group A. The plaques in group B were very small. In group C, obvious plaques were observed in the blood vessels, and the plaques exhibited a thin fibrous cap, a large lipid core, and partially visible neovascularization, which is consistent with the characteristics of vulnerable plaques. In the plaques of group C, a large number of macrophages were present, and matrix metalloproteinase 9 (MMP-9) and lectin-like oxidized LDL receptor 1 (LOX-1) were abundantly expressed. We successfully established a rabbit model of vulnerable carotid plaque similar to that of humans through the combination of cryofluid-induced endothelial injury and a high-fat diet, which is feasible and cost effective.


Assuntos
Modelos Animais de Doenças , Placa Aterosclerótica , Animais , Coelhos , Placa Aterosclerótica/patologia , Placa Aterosclerótica/etiologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Macrófagos/metabolismo , Macrófagos/patologia , Artérias Carótidas/patologia , Endotélio Vascular/patologia , Endotélio Vascular/metabolismo
18.
Front Psychol ; 15: 1161132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659681

RESUMO

In simple terms, consciousness is constituted by multiple goals for action and the continuous adjudication of such goals to implement action, which is referred to as the maps of meaning (MoM) consciousness theory. The MoM theory triangulates through three parallel corollaries: action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism's consciousness contains fluid, nested goals. These goals are not intentionality, but intersectionality, via the Darwinian byproduct of embodiment meeting the world, i.e., Darwinian inclusive fitness or randomization and then survival of the fittest. (2) These goals are formed via a gradual descent under inclusive fitness and are the abstraction of a "match" between the evolutionary environment and the organism. (3) Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience-crystallized efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one's adaptive environment. These efficiencies are objectively arbitrary but determine the operation and level of one's consciousness, termed as extreme thrownness. (4) Since inclusive fitness drives efficiencies in the physiologic mechanism, morphology, and behavior (action) and originates one's goals, embodiment is necessarily entangled to human consciousness as it is at the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. (5) Perception is the operant process of consciousness and is the de facto goal adjudication process of consciousness. Goal operationalization is fundamentally efficiency-based via one's unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. (6) Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception is not a 'frame rate' but Bayesian priors of efficiency based on one's extreme thrownness. (7) Consciousness and human consciousness are modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as the emergent phenomena at various modularities such as the stratified factors in factor analysis). (8) The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. (9) Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

19.
Front Psychol ; 15: 1163869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659691

RESUMO

Introduction: Although vegan and vegetarian diets and lifestyles differ significantly from each other, among other things, notably in their respective consequences regarding animal welfare and their ecological impact, vegans and vegetarians are often grouped together and usually compared to omnivores in psychological research. Considering that vegans and vegetarians often share similar motives for their lifestyle choices, namely animal and environmental issues, the question arises why similar motives lead to different conclusions and correspondingly different behaviors, most notably, of course, that vegetarians consume animal-derived foods such as cheese or milk while vegans do not consume animal-derived products (e.g., food, cosmetic products). This is why this study explored the psychological differences between vegans, vegetarians, and prospective vegans - the latter group being located in an intermediate, transitionary position. Focusing on the motivational, affective and cognitive components of dietary transition and participants' adherence to eating patterns, reasons for said patterns, possible hinderances to becoming vegan, the role of participants' social environments, and the impact of various misconceptions regarding the feasibility of a vegan diet in everyday life were all explored. Methods: An observational study was conducted via online questionnaire (1420 participants). Results: Significant differences were found between vegans, prospective vegans, and vegetarians, especially concerning their knowledge of issues pertaining to their respective lifestyles. Discussion: The critical role of knowledge is invoked as an explanation as to why vegans and vegetarians display different behaviors although they share a similar motivation. Thus, in this study the concept of vegan literacy is introduced. Additionally, the distinctive role of cheese is explored, discussing possible indications of its potentially addictive nature and, consequently, the importance of cheese as a hindering factor for pursuing a vegan diet.

20.
Sci Rep ; 14(1): 9159, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644372

RESUMO

Different strains of Escherichia coli that exhibit genetic characteristics linked to diarrhea pose a major threat to both human and animal health. The purpose of this study was to determine the prevalence of pathogenic Escherichia coli (E. coli), the genetic linkages and routes of transmission between E. coli isolates from different animal species. The efficiency of disinfectants such as hydrogen peroxide (H2O2), Virkon®S, TH4+, nano zinc oxide (ZnO NPs), and H2O2-based zinc oxide nanoparticles (H2O2/ZnO NPs) against isolated strains of E. coli was evaluated. Using 100 fecal samples from different diarrheal species (cow n = 30, sheep n = 40, and broiler chicken n = 30) for E. coli isolation and identification using the entero-bacterial repetitive intergenic consensus (ERIC-PCR) fingerprinting technique. The E. coli properties isolated from several diarrheal species were examined for their pathogenicity in vitro. Scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), Fourier-transform infrared spectrum (FT-IR), X-ray diffraction (XRD), zeta potential, and particle size distribution were used for the synthesis and characterization of ZnO NPs and H2O2/ZnO NPs. The broth macro-dilution method was used to assess the effectiveness of disinfectants and disinfectant-based nanoparticles against E. coli strains. Regarding the results, the hemolytic activity and Congo red binding assays of pathogenic E. coli isolates were 55.3 and 44.7%, respectively. Eleven virulent E. coli isolates were typed into five ERIC-types (A1, A2, B1, B2, and B3) using the ERIC-PCR method. These types clustered into two main clusters (A and B) with 75% similarity. In conclusion, there was 90% similarity between the sheep samples' ERIC types A1 and A2. On the other hand, 89% of the ERIC types B1, B2, and B3 of cows and poultry samples were comparable. The H2O2/ZnO NPs composite exhibits potential antibacterial action against E. coli isolates at 0.04 mg/ml after 120 min of exposure.


Assuntos
Galinhas , Diarreia , Desinfetantes , Infecções por Escherichia coli , Escherichia coli , Peróxido de Hidrogênio , Óxido de Zinco , Animais , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Peróxido de Hidrogênio/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Diarreia/microbiologia , Diarreia/veterinária , Galinhas/microbiologia , Desinfetantes/farmacologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Ovinos , Bovinos , Nanopartículas/química , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Fezes/microbiologia , Nanopartículas Metálicas/química
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