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Abstract Background Recent evidence suggests an elevated risk of cognitive impairment and dementia in individuals with atrial fibrillation (AF), irrespective of stroke occurrence. AF, known to reduce brain perfusion, particularly through silent cerebral ischemia, underscores the intricate relationship between cardiac and cerebral health. The heart plays a crucial role in supporting normal brain function, and rhythm control, a standard AF treatment, has demonstrated enhancements in brain perfusion. This systematic review aimed to examine published data concerning the influence of rhythm control on brain perfusion in patients with atrial fibrillation. Methods A systematic search for relevant studies was carried out in Scopus, PubMed, Cochrane Reviews, ProQuest, and EBSCOhost, spanning from their inception until April 30, 2023. Studies that specifically examined brain perfusion following any form of rhythm control in atrial fibrillation were included in the review. Results The review encompassed 10 studies involving 436 participants. Among these, six utilized electrical cardioversion for rhythm control. The majority (8 out of 10) demonstrated that restoring sinus rhythm markedly enhances brain perfusion. In one of the two remaining studies, notable improvement was observed specifically in a region closely linked to cognition. Additionally, both studies reporting data on the Mini‐Mental State Examination (MMSE) showed a consistent and significant increase in scores following rhythm control. Conclusion Successful rhythm control in AF emerges as a significant contributor to enhanced brain perfusion, suggesting a potential therapeutic avenue for reducing cognitive impairment incidence. However, further validation through larger prospective studies and randomized trials is warranted.

Quantum computing is a fascinating and rapidly evolving field of technology that promises to revolutionize many areas of science, engineering, and society. The fundamental unit of quantum computing is the quantum bit that can exist in two or more states concurrently, as opposed to a classical bit that can only be either 0 or 1. Any subatomic element, including atoms, electrons, and photons, can be used to implement qubits. The chosen sub-atomic elements should have quantum mechanical properties. Most commonly, photons have been used to implement qubits. Qubits can be manipulated and read by applying external fields or pulses, such as lasers, magnets, or microwaves. Quantum computers are currently suffering from various complications such as size, operating temperature, coherence problems, entanglement, etc. The realization of quantum computing, a novel paradigm that uses quantum mechanical phenomena to do computations that are not possible with classical computers, is made possible, most crucially, by the need for a quantum processor and a quantum SOC. As a result, Cryo-CMOS technology can make it possible to integrate a Quantum system on a chip. Cryo-CMOS devices are electronic circuits that operate at cryogenic temperatures, usually below 77 K (−196 °C).

Feedback should be beneficial to learners; it should provide information about their performance of a task or activity. This study aims to explore students' concerns and expectations toward teachers' online written feedback through photovoice. Participants involved fifteen students of a writing course. To obtain the data, a photovoice was used following Wang et al.'s SHOWeD protocols based on the theme "students' voices on teachers' online written feedback to promote discussion among participants and researchers about critical topics to generate solutions. Two instruments were used to collect the data; documentation in the form of the participants' photographs and a semi-structured interview with each participant. The result revealed that students had raised some points regarding the teacher's online written feedback. These points include: 1) online written feedback is sufficient; 2) online feedback should show the strength of students' writing; 3) students' revision will improve students writing quality; 4) students need a comfortable place, correct times, and snacks when revising. The study concludes that instead of simply making suggestions, as is customary when providing feedback, the students require the teacher's assessment of their strengths. The findings suggested that teachers and lecturers should consider the points when providing online written feedback to students.

The pandemic era pushed teachers to switch their teaching methods into online learning. The concept mapping strategy was one of the most effective teaching strategies for teaching English in face-o face mode . Is the concept mapping strategy still effective in online learning mode? This study utilized a quantitative approach to compare the use of concept mapping strategy and conventional strategy. Both classes did the instruction through hybrid flexible course. To obtain the data, test and observation were used. ANCOVA was performed to analyze the data to get the specific data concern to the effect of the strategy to the student grade. The findings showed that in the hybrid flexible course, concept mapping strategy did not impact the students’ achievement, but from the observation, it did impact the students’ motivation and activity during the instruction. It can be concluded that there is no significant difference of using concept mapping strategy and conventional strategy through hybrid flexible course

This research is intended as an effort to analyze the budget performance of Regional Apparatus Organizations in South Sumatra Province with a value for money concept approach. This study consisted of the dependent variable, namely the performance of the regional apparatus organization budget, while the independent variable consisted of transparency, accountability, and supervision. The data used in this research is the result of distributing questionnaires to selected respondents in 21 Regional Apparatus Organizations. The sample selection technique used purposive sampling, while the data analysis technique used multiple linear regression. The results of the analysis and discussion of hypothesis testing show that partially transparency, accountability, and supervision have a positive and significant effect on-budget performance, including simultaneously also showing a positive and significant effect on-budget performance, but it is necessary to increase budget performance, this shows that the R2 value is 0.446. or 44.6%.

Coronary computed tomographic angiography (CTA) is a non-invasive procedure that makes it very convenient to imagine the anatomical ability to remove coronary artery disease in patients with chest pain in a population at low to moderate risk. For plaque identification and physiological assessment, coronary CTA may be used, facilitating thorough diagnostic and prognostic assessment of primary prevention in patients. Overall plaque load is assessed by the coronary CTA, plaque subtypes are distinguished and high-risk plaque is identified. The purpose of this article is to review existing applications and practices related to the use of automatic techniques in coronary CTA analysis and interpretation.

It is fact that technology has a great impact and effect on learning processes. This article aims at verifying if students are able to learn and retain vocabulary just by watching videos. Over and over, students suggest the use of videos in the classroom, but are they really effective or are they only used for students’ entertainment? Based on authors such as Muslem (2017), Mc Nulty (2012) and Wang (2015), we realize that videos increase fluency and stimulate the appropriate pronunciation of English language learners. In addition, videos combine visual and audio stimuli, are accessible to those who have not learned to read and write well, and provide context for learning (Fazey, 1999; Johnston, 1999; Burt, 1999). In the first moment of this research, students are exposed to a quiz in which they have to choose the correct meaning for a certain word or phrase. In the second phase, the same pupils watch 5 different videos, chosen by them before the first quiz from a YouTube channel. Last but not least, students answer a questionnaire again to check how much they have learned and retained new vocabulary. We notice that, possibly, students do not learn new vocabulary just by being exposed to videos, without meaningful pre, while and post activities. Keywords: Additional Language Teaching. English vocabulary acquisition. Videos in classroom. RESUMO É fato que a tecnologia tem grande impacto e efeito nos processos de aprendizagem. Este artigo visa verificar se os alunos são capazes de aprender e reter vocabulário somente assistindo vídeos. Cada vez mais os alunos sugerem o uso de vídeos em sala de aula. Contudo, vídeos são realmente eficazes ou são usados somente para o entretenimento dos alunos? Baseado em autores como Muslem (2017) e Mc Nulty (2012), percebemos que vídeos melhoram a fluência e estimulam a pronúncia adequada dos aprendizes da língua inglesa. Além disso, vídeos combinam estímulo visual e sonoro, são acessíveis àqueles que ainda não aprenderam a escrever e ler adequadamente, e proporcionam contexto para a aprendizagem (Fazey, 1999; Johnston, 1999). No primeiro momento desta pesquisa, os alunos são expostos a um questionário no qual eles têm que escolher o significado correto de determinada palavra ou expressão. Na segunda fase, os mesmos estudantes assistem a 5 vídeos diferentes, escolhidos por eles, antes do primeiro questionário, de um canal do YouTube. Por último, os alunos respondem novamente ao questionário a fim de verificar o quanto eles aprenderam e retiveram o novo vocabulário. Percebemos que, possivelmente, os alunos não aprendem novas palavras de vocabulário somente através de sua exposição a vídeos, sem que realizem atividades relacionadas a eles antes, durante e depois de assisti-los. Palavras-chave: Ensino de língua adicional. Aquisição de vocabulário em língua inglesa. Vídeos em sala de aula.

Research on decision making and aging has shown that some decision-making skills decrease with age. Despite these age-related declines, no study has yet investigated the possibility of promoting improvements in decision-making skills in older adults. The present study was designed to address this gap in literature by examining the efficacy of a metacognitive-strategy decision-making training on practiced and non-practiced tasks. The training was based on the use of specific metacognitive principles and analytical strategies for promoting an analytical mode of thinking in the decision-making process. We examined 66 older adults (Mage= 67.52 years, SD = 5.38; age range 60-81) assigned to two training groups: a metacognitive-strategy decision-making training group and an active control group involved in a strategic memory intervention. Both training groups attended four 2-hour training sessions conducted once a week. Results showed that, after intervention, the decision-making training group improved their decision-making skills significantly more than the active control training group. Crucially, the positive effect of the training was evident in both practiced and non-practiced decision-making tasks. This is the first study investigating the efficacy of a decision-making training in older adults based on metacognitive and strategic principles.

Purpose Distance learning, which became widespread in response to the coronavirus disease 2019 (COVID-19) pandemic, has been a burdensome challenge for students and lecturers. This study investigated the relationship between academic self-efficacy and burnout in first-year nursing students who participated in distance learning during the COVID-19 pandemic. Methods The study included 69 first-year nursing students at Jenderal Achmad Yani University in Yogyakarta, Indonesia. Data were collected in September 2020 through self-efficacy and burnout questionnaires that were distributed via email and social media for 2 weeks. The responses were analyzed using the gamma test. Results Most respondents were women (78.3%), with an average age of 19 years. Most nursing students had a moderate level of academic self-efficacy (72.5%), while only 13.0% of respondents had a low level of academic self-efficacy. However, 46.4% of students experienced severe burnout during distance learning. Cross-tabulation showed that students with moderate self-efficacy were more likely to experience severe burnout (24 respondents) (P

Meaning-making choice place a significant position in written communication, as indirect contact needs a particular strategy to achieve the objective. This case study explores how female and male writers utilized their meaning-making choice through experiential meaning in their introduction part of journal article writing published in JEELL. Research articles written by five female writers and five male writers with English teachers' professional backgrounds are involved in this study. The results indicate that both female and male writers tend to use a particular process, such as material processes, to represent their real-world experiences of doing and happening. However, it is also found that there is a difference in the technique used in expressing material processes by female and male writers. The study also implies that male writers apply more verbal processes than female writers in citing or synthesizing sources. Furthermore, the investigations reveal that male writers produced more various type of mental processes than female writers.

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimers disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.

Several researchers have used metalinguistic tests as an effective way to provide data on the nature of language. Bley-Vroman et al. (1988), Hawkins e Chan (1997), Johnson e Newport (1989), Schachter (1989), Schütze (1996), White (2003), among others, have used those tests to support their hypothesis on the acquisition and the development of a second language (L2). In this article, we analyzed three researches with the aim of creating relevant conditions for producing metalinguistic tests (MT) to validate inquiries. Beyond that, we evaluate some tests, used in Second Language Acquisition, aiming to find out if the conditions presented in this research were satisfied. We point out, however, the tests used by some authors could have been built more carefully, so that they would be more trustful and achieve better validation of their results.

Pembentukan Reactive oxygen spesies (ROS) berperanan penting dalam kerusakan sel. ROS ini akan terus dikontrol oleh sistem antioksidan endogen, berupa antioksidan enzimatik ataupun non enzimatik. Antioksidan enzimatik adalah superoksida dismutase, katalase dan glutation peroksidase. Antioksidan non enzimatik adalah alfa tokoferol (vitamin E), asam askorbat (Vitamin C), glutation dan ubiquinon. Keseimbangan antara ROS dan antioksidan ini akan terus dipertahankan. Apabila terjadi peningkatan ROS yang berlebihan dan atau penurunan jumlah antioksidan yang di hasilkan tubuh baik akibat pengaruh faktor eksogen dan endogen, maka terjadi ketidakseimbangan antara antioksidan dan ROS. Hal ini menyebakan terjadinya keadaan patologis dan stess oksidatif. Antioksidan bekerja secara sinergis untuk menstabilkan peran ROS pada proses photoaging, karsinogenesis dan inflamasi. Terdapat berbagai ROS yang dihasilkan tubuh, masing-masing ROS ini dapat dinetralisir oleh antioksidan tertentu melalui suatu antioksidan network.

Today's increasingly rapid technological developments do not only appear in the field of communication but are also needed in education. In the education field, it is expected to instill students with adequate knowledge and critical thinking skills, which are needed for their future. Practicing critical thinking skills can be done with mobile applications because today's students are highly familiar with gadgets. In terms of education, students need a learning platform that is equipped with audio, images, and easy-to-understand text. To accommodate this, an Android-based application was designed to provide learning steps, such as analyzing, obtaining information, asking questions, and making conclusions. This study is a qualitative descriptive study using the ADDIE (analyzing, designing, developing, implementing, and evaluating) method. It includes material analysis, application design with smart apps creator (SAC), testing by media and materials experts, and overall evaluation. The trial of this application was carried out on 3rd-grade elementary school students with questionnaires and interviews. Based on the validation process by IT experts and elementary school teachers, the development of the situation-based learning (SBL) App was considered valid. In other words, this application was properly designed according to the development of lower-grade students. Furthermore, the students were interested in SBL App and found it easier to obtain information, come up with good questions, and draw conclusions from a material using the app. Therefore, it can be concluded that the SBL App developed in this study is feasible and effective to be used as an Android-based learning application to train elementary school students' critical thinking skills.

This paper discusses an experiment conducted with two groups of participants, composed of musicians and non-musicians, in order to investigate the impact that the speed of a sound sequence and the interval size which selected sounds are played on the grouping of sounds into perceptual streams. Significant differences were observed between musicians and non-musicians with respect to the threshold sequence speed at which the sequence was split into two streams. In modern psychoacoustic studies, the qualifying criteria for listeners usually include otologically normal hearing (verified by audiometric test) and age. The differences in the results for the two groups suggest that the musical background of the participating listeners may be a vital factor. The criterion of musical education should be taken into account during experiments so that the results obtained are reliable, uniform and free from interpretive errors.

Abstract Resource scarcity, the effects of climate change, food insecurity, and health issues related to dietary choices have prompted policymakers to develop new strategies to encourage populations to opt for healthy and sustainable (HS) diets. In this context, nudging strategies are promising tools to promote healthy and sustainable dietary behaviors. However, nudges are context-dependent as a specific nudging intervention should be employed in a specific context. This research aims at determining the effects of different nudges on students’ food choices in the context of a hypothetical online pre-ordering system of the college canteen. An experimental study was conducted in the USA with 1400 American college students (18–24 years old). We used a between-subject design with one control and three treatment groups—i.e., a HS logo to identify HS dishes, dish placement (the order in which dishes are displayed on the menu), and a combination of the two nudges. Our main results showed that the logo and logo plus placement led to a significantly increased selection of HS dishes among students who already had strong HS eating behaviors. In addition, individual characteristics (e.g., being flexitarian or vegetarian, being on a low-calorie diet, being a graduate student, and living in dormitories on college campuses) also affected their HS food choices; thus, the population traits, living conditions, and eating habits should be taken into consideration in order to establish successful nudging techniques.

As the number of occurrences of skin cancer increases year, it becomes more and more crucial to identify the disease accurately and effectively. This study aims to implement and evaluate the MobileNet architecture for classifying nine types of skin lesions using the ISIC 2020 dataset and to compare MobileNet's performance with other CNN architectures, such as VGG-16 and LeNet, in terms of accuracy and computational efficiency. The study also investigates the impact of image preprocessing on model accuracy. The methodology comprises data collection, preprocessing, and model development, leveraging transfer learning from MobileNet pre-trained on ImageNet. Data preprocessing involves resizing images to 224 x 224 pixels and normalizing pixel values. To augment the dataset, techniques such as rotation, zooming, horizontal flipping, and brightness and contrast adjustment are applied. To address class imbalance, oversampling is used to obtain 500 images per class. The model architecture includes Global Average Pooling, a Dense layer with 1024 units and ReLU activation, and a Dropout layer with a 0.2 probability. Various training scenarios with batch sizes (8, 16, 32, 64) and learning rates (0.001, 0.0001) are evaluated, incorporating dropout and ReLU activations. The optimal performance was achieved with oversampling, dropout, and a learning rate of 0.0001, yielding a training accuracy of 99.64% and a validation accuracy of 86.89% after oversampling, resulting in 3,600 training and 900 validation images with an 80:20 data split. The results suggest overfitting due to dataset limitations. Future work should focus on fine-tuning and ensemble methods to improve validation performance.

Introduction: Numerous studies have examined the precursors and personal traits associated with deviant behavior, but little is known about normative attitudes. This study aimed to conduct an exploratory survey on the perception and moral beliefs about deviant behavior. Methods: We collected data from 100 students belonging to two high schools in Calabria, Southern Italy, to whom was administered a revised version of the Italian version of the International Self-Reported Delinquency (ISRD-3) questionnaire and a self-rating scale for the moral evaluation of deviant behavior. Results: In our sample, deviant adolescents were less than 5%. However, it was possible to collect attitudes by drawing graffiti, illegally downloading from the internet, making their own justice, and signaling the police car. It has also emerged as difficult to correctly conceptualize and categorize rights and duties. Conclusions: Our results, discussed in the light of the literature, provide to policy-mahers and researchers helpful information on the most prevalent attitudes among adolescents in Southern Italy.

O objetivo principal deste trabalho é discutir as percepções de professores de inglês como língua estrangeira acerca de como a internet e as novas tecnologias têm influenciado na aprendizagem de línguas, tanto em sala de aula como em ambientes informais. Autores como ZHAO (2005), LAI (2005) e STANLEY (2012) percebem que o uso de blogs, chats, tweeter, e-mails, sites e vídeos da internet, entre outros, podem contribuir para uma aprendizagem mais eficaz da língua inglesa. Portanto não é surpresa observar que, nesta pesquisa, a maioria dos professores de inglês entrevistados acredita que as novas tecnologias podem mudar a maneira como se aprende e se ensina línguas estrangeiras.

Localizing sounds in noisy environments can be challenging. Here, we reproduce real-life soundscapes to investigate the effects of environmental noise on sound localization experience. We evaluated participants' performance and metacognitive assessments, including measures of sound localization effort and confidence, while also tracking their spontaneous head movements. Normal-hearing participants (N = 30) were engaged in a speech-localization task conducted in three common soundscapes that progressively increased in complexity: nature, traffic, and a cocktail party setting. To control visual information and measure behaviors, we used visual virtual reality technology. The results revealed that the complexity of the soundscape had an impact on both performance errors and metacognitive evaluations. Participants reported increased effort and reduced confidence for sound localization in more complex noise environments. On the contrary, the level of soundscape complexity did not influence the use of spontaneous exploratory head-related behaviors. We also observed that, irrespective of the noisy condition, participants who implemented a higher number of head rotations and explored a wider extent of space by rotating their heads made lower localization errors. Interestingly, we found preliminary evidence that an increase in spontaneous head movements, specifically the extent of head rotation, leads to a decrease in perceived effort and an increase in confidence at the single-trial level. These findings expand previous observations regarding sound localization in noisy environments by broadening the perspective to also include metacognitive evaluations, exploratory behaviors and their interactions.

Nowadays the educational paradigm has changed from passive learning into active learning where learners are actively involved in teaching and learning process. Internet, as one of the information and communication products, is believed to be able to facilitate an active and interactive teaching and learning process. One of the examples is the use of Learning Management System (LMS). LMS is viewed appropriate to be applied in teaching English especially the writing skill in which learners need more time and more exercises to improve their skills. The limited time of classroom meeting makes the need impossible to be fulfilled. By using LMS, the teaching and learning process can not only depend on the classroom meeting but also can be done outside the classroom anytime and anywhere. In this quasi-experimental research the researchers were eager to know the effectiveness of active learning by using LMS to improve students’ writing skill, especially in argumentative writing. The data was analyzed with ANCOVA using SPSS version 20. The result shows that the value of F-value is 5.505 and the significant value is .021 which is less than .05, and the F-value is higher than F-table (3.94). It means that the alternative hypothesis (Ha) is accepted. Thus, it can be concluded that teaching writing by using LMS is more effective than conventional classroom meeting.

Pencitraan kardiak non-invasif dengan teknologi tomografi komputer multi-potongan telah menempati peranan penting dalam diagnosis penyakit jantung dan pembuluh darah. Di Indonesia, penggunaan tomografi komputer kardiak (TKK) telah meluas di kota-kota besar. Panduan yang menjadi standar pelayanan TKK di Indonesia diperlukan agar dokter yang melakukan interpretasi di seluruh Indonesia melaporkan interpretasinya dalam struktur yang seragam sehingga mudah dipahami oleh dokter pengirim. Hal ini menjamin pelayanan terbaik dan keamanan bagi pasien, dokter, dan fasilitas kesehatan, serta menjadi acuan kualitas pelayanan TKK yang berlaku di seluruh Indonesia. Standarisasi ini tentu bermanfaat untuk pendidikan dan penelitian serta penelaahan sejawat.

PURPOSE: To analyze the effects of application of 1% and 3% insulin-like growth factor I (IGF-1) cream on the process of wound healing in induced skin lesions in diabetic and non-diabetic rats and evaluate its effect on expression of myofibroblasts.METHODS: Ninety-six Wistar adult male rats were divided into six groups, with 16 rats in each group, as follows: group 1: non-diabetic, untreated; group 2: non-diabetic, treated with 1% IGF-1 cream; group 3: non-diabetic, treated with 3% IGF-1 cream; group 4: diabetic, untreated; group 5: diabetic, treated with 1% IGF-1 cream; and group 6: diabetic, treated with 3% IGF-1 cream. In groups 4, 5, and 6, diabetes was induced by intravenous injection of alloxan. After diabetes had been induced, animals were mantained for 3 months. The experimental procedure consisted of the creation of a circular incision of 0.9 mm in diameter using a metal punch. Following this, wounds were treated daily according to the assigned treatment regimen. Groups 2 and 5 were treated with 1% IGF-1 cream, groups 3 and 6 with 3% IGF-1 cream, and groups 1 and 4 and the untreated groups with 0.9% saline solution. From each group, samples from 4 rats were taken at three, seven, 14, and 21 days after the injury. Samples were fixed in 10% formalin to prepare slides for histological analysis. Slides stained with hematoxylin-eosin (H&E) and Masson were observed vascular proliferation, mononuclear cells, polymorphonuclear cells, fibroblast proliferation, re-epithelialization, and collagen fibers. This study analyzed the expression of α-smooth muscle actin using specific antibodies to correlate the temporal expression of α-smooth muscle-specific actin (α-SM actin), a molecular marker for myofibroblast transformation.RESULTS:Macroscopic observation of wounds showed a more rapid re-epithelialization of wounds treated with IGF. Regarding acute inflammatory reactions, the results of the analysis of vascular proliferation and polymorphonuclear and mononuclear cells showed no statistically significant differences in any of the periods studied (according to the results of a Mann-Whitney test). The initial immunohistochemical analysis of tissue samples conducted to compare the expression of α-smooth muscle actin between groups showed a relevant response in the expression of myofibroblasts. Data were analyzed using ANOVA and were found to be statistically significant.CONCLUSION: The topical application of 1% and 3% IGF-1 creams increases the expression of myofibroblasts in the process of wound healing in rats.