"Chemobrain" in childhood cancer survivors-the impact on social, academic, and daily living skills: a qualitative systematic review.

PURPOSE: To examine children's experiences of chemotherapy-induced cognitive impairment--colloquially "chemobrain"--and the impact on children's social, academic, and daily living skills via a qualitative systematic review. Experiencing chemotherapy as a child, when the brain is still developing, may cause lifelong detriment to survivors' lives. There is a significant gap in understanding their lived experience, including the self-identified barriers that children face following treatment. Such a gap can only be fully bridged by listening to the child's own voice and/or parent proxy report through an exploration of the qualitative research literature. METHODS: A search of MEDLINE, Embase, PsycINFO, and CINAHL databases was conducted. Inclusion criteria were qualitative studies with a focus on children (0-18 years) during and/or following chemotherapy treatment and explored children's experiences of chemobrain. RESULTS: Two synthesized findings were identified from six studies. (1) Chemobrain has an academic and psychosocial impact, which may not be understood by education providers. (2) Children and their parents have concerns about their reintegration and adaptation to school, social lives, and their future selves as independent members of society. Children's experiences primarily related to changes in their academic and social functioning. CONCLUSION: This review highlights two important considerations: (1) the lived experiences of pediatric childhood cancer survivors guiding where future interventions should be targeted, and (2) a need to perform more qualitative research studies in this area, as well as to improve the quality of reporting among the existing literature, given that this is a current gap in the field.

Neuroimmune reactivity marker expression in rodent models of chemotherapy-induced cognitive impairment: A systematic scoping review.

BACKGROUND: Chemotherapy-induced cognitive impairment (CICI) is a debilitating side effect arising from chemotherapy treatments. The condition is characterised by a range of cognitive deficits including impairment to memory, attention, and concentration. Whilst the underlying mechanisms that contribute to CICI remain unclear, neuroinflammation has been suggested as one key contributor. METHOD: A comprehensive systematic search of EMBASE and Medline via PubMed was conducted to identify studies on neuroimmune reactivity marker expression changes and resulting cognitive changes in preclinical rodent models of CICI. RESULTS: A total of twenty studies met the eligibility criteria and were included in the scoping review. There was significant heterogeneity in the methodology employed in the included studies. Our findings demonstrate that widespread changes in cytokines, chemokines, microglia reactivity, and astrocyte reactivity are observed in CICI in the brain regions expected to be affected, given the nature of the cognitive impairment observed in CICI. CONCLUSIONS: Although there was considerable heterogeneity in study design that made comparisons between studies difficult, our findings suggest that neuroinflammation commonly occurs in CICI preclinical rodent models and shows an association with cognitive impairment.

Reporting in rodent models of 'chemobrain': a systematic review assessing compliance with the ARRIVE guidelines.

Patients diagnosed with cancer are often plagued with debilitating side effects post-chemotherapy treatment. One such side effect is chemotherapy-induced cognitive impairment or 'chemobrain'. Rodent models are commonly used to investigate pathogenesis and potential therapeutic strategies. However, concerns have been raised regarding inadequacies in reporting of animal studies rendering them unreliable and irreproducible. The aim of this systematic review was to assess compliance with the ARRIVE reporting guidelines in peer-reviewed publications evaluating chemotherapy-induced cognitive changes in rodent models, and to determine if the introduction of the ARRIVE guidelines has improved quality of reporting. A comprehensive search was conducted to identify relevant peer-reviewed publications. Ninety-seven studies met the eligibility criteria, and publication compliance with the ARRIVE guideline reporting was assessed. No studies achieved full adherence with the ARRIVE guidelines. Furthermore, no significant improvement was demonstrated in the overall compliance score post-ARRIVE. Given the lack of standardisation of animal models in this research area, these results pose particular threat to future progress and translation of findings in this area of research. These results highlight the need for stricter adherence to the ARRIVE guidelines by journal editors and reviewers. Animal Ethics Committees also have an important educative role in improving knowledge and awareness of the guidelines amongst researchers.

Oral Nucleotides Only Minimally Improve 5-Fluorouracil-Induced Mucositis in Rats.

Chemotherapy-induced mucositis is characterized by inflammation and ulceration of the intestinal mucosa, compromising intestinal function. Exogenous nucleotides have been reported to repair the mucosa. The nucleotide preparation, Nucleoforce F0328 (Nucleoforce), was investigated for its potential to ameliorate intestinal mucositis in rats. Female Dark Agouti rats (n = 8/group) were gavaged once daily with Nucleoforce (175 mg/kg) or water from Days 0 to 8 and injected (i.p.) with 5-fluorouracil (5-FU; 150 mg/kg) or saline on Day 5. Histological parameters (disease severity, crypt depth, and villus height measurements) and myeloperoxidase activity were quantified. P < 0.05 was considered significant. Jejunal and ileal histological disease severity scores were significantly increased by 5-FU, compared to normal controls (P < 0.05). Nucleoforce treatment in 5-FU-injected rats significantly reduced jejunal and ileal disease severity compared to 5-FU controls (P < 0.05). In 5-FU-injected rats, jejunal and ileal villus heights and crypt depths were significantly decreased compared to 5-FU controls, with no additional Nucleoforce effect (P > 0.05). Intestinal myeloperoxidase activity was significantly elevated by 5-FU (8.8-fold), compared to normal controls (P < 0.05), which was not normalized by Nucleoforce treatment (P > 0.05). Nucleoforce only partially improved parameters associated with experimentally-induced mucositis. Future studies could investigate increased concentrations, more frequent administration, or protective microencapsulation delivery methods, to increase bioavailability.

Incorporation of a stand-alone elective course in animal law within animal and veterinary science curricula.

Animal law is a burgeoning area of interest within the legal profession, but to date it seems to have received little attention as a discrete discipline area for animal and veterinary scientists. Given the increased focus on animal welfare both within curricula and among the public, it would be remiss of educators not to consider this allied subject, especially since it provides those tools necessary for implementing welfare standards and reducing cruelty. Recommended subject matter, teaching modality, and methods of assessment have been outlined in this article. Such a course should take a multidisciplinary approach and highlight contentious areas of animal law and trends within the wider societal framework of human-animal interactions. From a pedagogical standpoint, a variety of teaching methods and assessment techniques should be included. A problem-based learning approach to encourage the assimilation of facts and promote higher-order learning is favored. The purpose of this article is to provide some guidance on the structure of such a course based on the author's experience in teaching animal law to veterinary and animal science undergraduates in Australia.

Tactile, Auditory, and Visual Stimulation as Sensory Enrichment for Dairy Cattle.

Several types of enrichment can be used to improve animal welfare. This review summarizes the literature on the use of mechanical brushes, tactile udder stimulation, music, and visual stimuli as enrichment methods for dairy cows. Mechanical brushes and tactile stimulation of the udder have been shown to have a positive effect on milk yield and overall behavioral repertoire, enhancing natural behavior. Classical music reduces stress levels and has similarly been associated with increased milk yield. A slow or moderate tempo (70 to 100 bpm) at frequencies below 70 dB is recommended to have this positive effect. Evidence on the impacts of other types of enrichment, such as visual stimulation through mirrors, pictures, and color lights, or the use of olfactory stimuli, is equivocal and requires further study.

Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

BACKGROUND: Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. AIMS: The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. METHODS: Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. RESULTS: Body weight was significantly decreased by doxorubicin compared with normal controls (p < 0.05). Histological parameters, such as crypt depth and villus height, were also significantly decreased by doxorubicin. TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. CONCLUSIONS: The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

A policy at the University of Adelaide for student objections to the use of animals in teaching.

In veterinary medical education, the use of animals or cadaveric tissue as a component of teaching practice is common. Teachers are required, during the process of ethical review, to apply the 3 Rs principle (replacement, refinement, reduction) whenever they consider using animals during a teaching exercise. This often involves use of replacement strategies, such as utilization of video footage or simulation-based training. However, aside from legislative or ethical requirements imposed by a country's regulatory framework on the institution, students are often the key advocates for using alternative teaching practices that do not make use of animals. This has prompted many institutions with veterinary and other life sciences teaching programs to develop student-conscientious objection policies to the use of animals in teaching. In this article, we discuss the procedures implemented to make provision for student-conscientious objectors at a new Australian Veterinary School, at the University of Adelaide. We also describe the processes to provide information to students and faculty on this issue and to facilitate information gathering on alternatives.

How Well Does Australian Animal Welfare Policy Reflect Scientific Evidence: A Case Study Approach Based on Lamb Marking.

The development and substance of animal welfare policy is subject to a range of social, cultural, economic, and scientific influences that commonly vary within and between countries. Discrepancies in policy can create confusion and mistrust among stakeholders and consumers and limit the ability to create a uniform minimum level of requirements to safeguard animal welfare, as well as create a level 'playing field' for farmers when trading with other jurisdictions. The livestock sector is receiving growing scrutiny globally for real and perceived violations of animal welfare, for example, the practice of mulesing in Australia. This article explores animal welfare legislation within Australia and how it reflects the scientific evidence surrounding routine husbandry practices in sheep, including tail docking, castration, and mulesing. While there is some variation between state and territory legislation, the most notable concern is the lack of enforceable recommendations surrounding the evidence-based use of analgesia and anaesthesia for painful husbandry procedures. The age at which these procedures are recommended to be performed is relatively consistent across Australian jurisdictions, but there is a marked difference compared to international legislation. The global context of animal welfare legislation, public perception, and producer perception of these procedures are also discussed, highlighting the difficulty of creating robust animal welfare legislation that promotes a good standard of welfare that is respected worldwide whilst being practical in an Australian setting given our unique geography and climatic conditions.

The Impact of Vegan Diets on Indicators of Health in Dogs and Cats: A Systematic Review.

There has been an increase in vegetarianism and veganism in human populations. This trend also appears to be occurring in companion animals, with guardians preferring to feed their animals in accordance with their own dietary values and choices. However, there has been controversy amongst vets and online commentators about the safety of feeding vegan diets to carnivorous species, such as cats and dogs. In spite of this controversy, to date there has been no systematic evaluation of the evidence on this topic. A systematic search of Medline, Scopus, and Web of Science was performed, identifying 16 studies on the impact of vegan diets on cat and dog health. Studies were appraised for quality using established critical appraisal tools or reporting guidelines. There was considerable heterogeneity in the outcomes measured, and study designs employed, with few studies evaluating key outcomes of interest. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was utilized for assessment of certainty in the evidence, with the evidence for most outcomes being assessed as low or very low. Whilst the quality and amount of evidence needs to be considered in formulating recommendations, there was no overwhelming evidence of adverse effects arising from use of these diets and there was some evidence of benefits. It is, however, recommended that future high-quality studies, with standardized outcome measures and large sample sizes, be conducted. At the current time, if guardians wish to feed their companion animals vegan diets, a cautious approach should be taken using commercially produced diets which have been formulated considering the nutritional needs of the target species.

The effectiveness of anti-inflammatory agents in reducing chemotherapy-induced cognitive impairment in preclinical models - A systematic review.

Chemotherapy-induced cognitive impairment (CICI) is a debilitating condition resulting from chemotherapy administration for cancer treatment. CICI is characterised by various cognitive impairments, including issues with learning, memory, and concentration, impacting quality of life. Several neural mechanisms are proposed to drive CICI, including inflammation, therefore, anti-inflammatory agents could ameliorate such impairments. Research is still in the preclinical stage; however, the efficacy of anti-inflammatories to reduce CICI in animal models is unknown. Therefore, a systematic review was conducted, with searches performed in PubMed, Scopus, Embase, PsycInfo and Cochrane Library. A total of 64 studies were included, and of the 50 agents identified, 41 (82%) reduced CICI. Interestingly, while non-traditional anti-inflammatory agents and natural compounds reduced impairment, the traditional agents were unsuccessful. Such results must be taken with caution due to the heterogeneity observed in terms of methods employed. Nevertheless, preliminary evidence suggests anti-inflammatory agents could be beneficial for treating CICI, although it may be critical to think beyond the use of traditional anti-inflammatories when considering which specific compounds to prioritise in development.

Assessment of Pain and Inflammation in Domestic Animals Using Infrared Thermography: A Narrative Review.

Pain assessment in domestic animals has gained importance in recent years due to the recognition of the physiological, behavioral, and endocrine consequences of acute pain on animal production, welfare, and animal model validity. Current approaches to identifying acute pain mainly rely on behavioral-based scales, quantifying pain-related biomarkers, and the use of devices monitoring sympathetic activity. Infrared thermography is an alternative that could be used to correlate the changes in the superficial temperature with other tools and thus be an additional or alternate acute pain assessment marker. Moreover, its non-invasiveness and the objective nature of its readout make it potentially very valuable. However, at the current time, it is not in widespread use as an assessment strategy. The present review discusses scientific evidence for infrared thermography as a tool to evaluate pain, limiting its use to monitor acute pain in pathological processes and invasive procedures, as well as its use for perioperative monitoring in domestic animals.

Controversial Topics in Animal Welfare in Latin America: A Focus on the Legislation Surrounding the Human-Companion Animal Relationship and Animals Used for Recreational Practices.

Animal welfare is a societally relevant issue that is globally attracting increased attention. This is in addition to the importance placed on welfare for the animals themselves. However, the content and application of laws protecting animals' welfare vary across countries. In Latin America, there are a range of common practices or activities involving certain animal species, many of which are legal, that can impair an animal's quality of life. These include the performance of aesthetic surgical procedures; bull-, cock-, and dog fighting; and the existence of circuses that exhibit animals. The extent and impact of these practices being dependent on the socioeconomic, cultural, territorial, and regulatory landscape of each country. Particularly, Ibero-American regions face welfare challenges that might be influenced by traditions and relevant legal gaps. The objective of this article is to review controversial practices carried out in companion and entertainment animals in Latin America, with a focus on legal aspects, as well as the current efforts being made to address and incorporate global welfare standards into domestic and wild animal practice and regulation.

Understanding Subordinate Animal Welfare Legislation in Australia: Assembling the Regulations and Codes of Practice.

The state-based approach to regulating animal welfare in Australia is thought to create national dis-uniformity in that each state and territory legislates and operates inconsistently. The animal welfare legal framework in each of the eight Australian jurisdictions is made up of a primary statute and subordinate legislation, where subordinate animal welfare legislation, in the forms of regulations and codes of practices, are lower-ranking laws that are given power under the jurisdiction's specific animal welfare statute. Since a review of animal welfare statutes identified broad patterns between the jurisdictions, this study is intended to be complementary by collating the subordinate legislation to provide a more comprehensive understanding of animal welfare laws in Australia. Using targeted search strategies stemming from the eight enabling animal welfare statutes, this study identified 201 pieces of subordinate legislation in force between 28 March 2022 and 5 April 2022. The scope of subordinate legislation is depicted through the following utility categories of animals: companion, production, wild/exotic, entertainment. Whilst subordinate legislation differed between the jurisdictions, it was common for similar welfare concerns or topic areas to be protected in higher-order legislation (statutes or regulations). Additionally, many jurisdictions were found to have similar shortcomings, all which likely could be managed through a mechanism of national data collection.

Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis.

Breast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequel of treatment is chemotherapy-induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers, hence a systematic review of prevalence data was performed. Medline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests. The review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21-34% respectively (very low GRADE evidence). Synthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.

Portraying Animal Cruelty: A Thematic Analysis of Australian News Media Reports on Penalties for Animal Cruelty.

Media portrayals of animal cruelty can shape public understanding and perception of animal welfare law. Given that animal welfare law in Australia is guided partially by 'community expectations', the media might indirectly be influencing recent reform efforts to amend maximum penalties in Australia, through guiding and shaping public opinion. This paper reports on Australian news articles which refer to penalties for animal cruelty published between 1 June 2019 and 1 December 2019. Using the electronic database Newsbank, a total of 71 news articles were included for thematic analysis. Three contrasting themes were identified: (1) laws are not good enough; (2) laws are improving; and (3) reforms are unnecessary. We propose a penalty reform cycle to represent the relationship between themes one and two, and 'community expectations'. The cycle is as follows: media reports on recent amendments imply that 'laws are improving' (theme two). Due to a range of inherent factors in the criminal justice system, harsher sentences are not handed down by the courts, resulting in media report of 'lenient sentencing' (theme one). Hence, the public become displeased with the penal system, forming the 'community expectations', which then fuel future reform efforts. Thus, the cycle continues.

Welfare Assessment Tools in Zoos: From Theory to Practice.

Zoos are increasingly implementing formalized animal welfare assessment programs to allow monitoring of welfare over time, as well as to aid in resource prioritization. These programs tend to rely on assessment tools that incorporate resource-based and observational animal-focused measures. A narrative review of the literature was conducted to bring together recent studies examining welfare assessment methods in zoo animals. A summary of these methods is provided, with advantages and limitations of the approaches presented. We then highlight practical considerations with respect to implementation of these tools into practice, for example scoring schemes, weighting of criteria, and innate animal factors for consideration. It is concluded that there would be value in standardizing guidelines for development of welfare assessment tools since zoo accreditation bodies rarely prescribe these. There is also a need to develop taxon or species-specific assessment tools to complement more generic processes and more directly inform welfare management.

The Neuroimmune Interface and Chronic Pain Through the Lens of Production Animals.

Communication between the central nervous system (CNS) and the immune system has gained much attention for its fundamental role in the development of chronic and pathological pain in humans and rodent models. Following peripheral nerve injury, neuroimmune signaling within the CNS plays an important role in the pathophysiological changes in pain sensitivity that lead to chronic pain. In production animals, routine husbandry procedures such as tail docking and castration, often involve some degree of inflammation and peripheral nerve injury and consequently may lead to chronic pain. Our understanding of chronic pain in animals is limited by the difficulty in measuring this pathological pain state. In light of this, we have reviewed the current understanding of chronic pain in production animals. We discuss our ability to measure pain and the implications this has on animal welfare and production outcomes. Further research into the neuroimmune interface in production animals will improve our fundamental understanding of chronic pain and better inform human clinical pain management and animal husbandry practices and interventions.

Impact of "chemobrain" in childhood cancer survivors on social, academic, and daily living skills: a qualitative systematic review protocol.

OBJECTIVE: The objective of this review is to examine children's experiences of chemotherapy-induced cognitive impairment (also known as "chemobrain") and the impact of chemobrain on children's social, academic, and daily living skills. INTRODUCTION: The effect of childhood chemotherapy treatment on cognition is of concern because of the vulnerable nature of children's developing brains and the potential to cause lifelong detriments socially, academically, and economically. Furthermore, this population is under-represented in the chemobrain literature and in survivorship care plans. As cancer survivorship among this group increases, it is important to understand childhood experiences so that rehabilitation strategies and suitable supports can be put in place. INCLUSION CRITERIA: This review of qualitative studies will focus on the pediatric population (0 to 18 years of age) during and/or following chemotherapy treatment to identify their experiences with chemobrain. The review will include any studies using a qualitative research methodology (eg, surveys, focus groups, interview transcripts), conducted in any geographic location, where experiences are presented from the child's perspective. Studies assessing children's experiences of cancer, other chemotherapy-related side effects, or the parent's personal experience will be excluded. METHODS: A search of MEDLINE, Embase, PsycINFO, and CINAHL databases will be conducted. Full-text, English-only articles employing a qualitative research methodology will be included in the screening process. Two independent reviewers will retrieve and screen full-text studies, and assess methodological quality of the included studies. Meta-aggregation will be performed and a ConQual Summary of Findings will present the confidence in the findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021240573.

The neurobiology of pain and facial movements in rodents: Clinical applications and current research.

One of the most controversial aspects of the use of animals in science is the production of pain. Pain is a central ethical concern. The activation of neural pathways involved in the pain response has physiological, endocrine, and behavioral consequences, that can affect both the health and welfare of the animals, as well as the validity of research. The strategy to prevent these consequences requires understanding of the nociception process, pain itself, and how assessment can be performed using validated, non-invasive methods. The study of facial expressions related to pain has undergone considerable study with the finding that certain movements of the facial muscles (called facial action units) are associated with the presence and intensity of pain. This review, focused on rodents, discusses the neurobiology of facial expressions, clinical applications, and current research designed to better understand pain and the nociceptive pathway as a strategy for implementing refinement in biomedical research.