Systematic Review Of Animal Models Research Articles

Effects of Laser Photobiomodulation on the Regeneration of Bone Defects Grafted with Bio-Oss® Xenograft: a Systematic Review of Animal Models

Abstract Photobiomodulation with low-power laser has stood out for its effects on metabolism, bone regeneration and its notable osteogenic potential. This study aimed to review the literature regarding the effectiveness of photobiomodulation with low-level laser therapy (LLLT) in inducing bone regeneration in sites grafted with Bio-Oss®, through experimental animal studies. It was a systematic review, based on a search performed in PubMed/Medline, Google Scholar, Capes Journals, SciELO and BIREME databases. Descriptors were selected from DeCS/MeSH and the PICOS strategy was applied. Experimental studies published from 2012 to 2023 were included, according to the PRISMA parameters, registered in the PROSPERO platform. The SYRCLE risk of bias tool was used. Using the search strategy, 1352 articles were identified, and five were included in this qualitative synthesis. Despite the divergence observed in the laser dosimetry protocols adopted by the studies, it was evident that laser photobiomodulation associated with the use of Bio-Oss® promotes bone density gains and a considerable increase in the amount of mineralized tissue in bone defects induced in animals. In addition, the use of laser alone has contributed to an improvement in bone formation in non-grafted sites. The data presented show a potential for improvement in the bone reconstruction process by associating photobiomodulation with low-level laser with the application of the Bio-Oss® inorganic bovine bone xenograft. Keywords: Low-Level Laser Therapy. Photobiomodulation Therapy. Xenografts. Bio-Oss. ResumoA fotobiomodulação com laser de baixa potência tem se destacado pelos seus efeitos no metabolismo, na regeneração óssea e por seu notável potencial osteogênico. Este estudo teve como objetivo revisar a literatura sobre a eficácia da fotobiomodulação com laserterapia de baixa potência (LLLT) na indução da regeneração óssea em locais enxertados com Bio-Oss®, por meio de estudos experimentais em animais. Trata-se de uma revisão sistemática, baseada em busca realizada nas bases de dados PubMed/Medline, Google Acadêmico, Periódicos Capes, SciELO e Bireme. Os descritores foram selecionados no DeCS/MeSH e aplicada a estratégia PICOS. Foram incluídos estudos experimentais publicados de 2012 a 2023, segundo parâmetros PRISMA, cadastrados na plataforma PROSPERO. Foi utilizada a ferramenta de risco de viés SYRCLE. Utilizando a estratégia de busca, foram identificados 1.352 artigos, e cinco foram incluídos nesta síntese qualitativa. Apesar da divergência observada nos protocolos de dosimetria do laser adotados pelos estudos, ficou evidente que a fotobiomodulação laser associada ao uso do Bio-Oss® promove ganhos de densidade óssea e aumento considerável na quantidade de tecido mineralizado em defeitos ósseos induzidos em animais. Além disso, o uso isolado do laser contribuiu para uma melhora na formação óssea em locais não enxertados. Os dados apresentados mostram potencial de melhoria no processo de reconstrução óssea através da associação da fotobiomodulação com laser de baixa intensidade com a aplicação do xenoenxerto ósseo bovino inorgânico Bio-Oss®. Palavras-chave: Terapia com Luz de Baixa Intensidade. Terapia de Fotobiomodulação. Xenoenxertos. Bio-Oss.

Evaluating and developing sealants for the prevention of pulmonary air leakage: A systematic review of animal models.

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included (N = 75 experiments, N = 1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N = 5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.

Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies

Study designSystematic review.BackgroundAlthough degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models.MethodsMEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14).ResultsThe search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models.ConclusionFew human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach.

Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.

Antidepressants (ADs) are, for now, the best everyday treatment we have for moderate to severe major depressive episodes (MDEs). ADs are among the most prescribed drugs in the Western Hemisphere; however, the trial-and-error prescription strategy and side-effects leave a lot to be desired. More than 60% of patients suffering from major depression fail to respond to the first AD they are prescribed. For those who respond, full response is only observed after several weeks of treatment. In addition, there are no biomarkers that could help with therapeutic decisions; meanwhile, this is already true in cancer and other fields of medicine. For years, many investigators have been working to decipher the underlying mechanisms of AD response. Here, we provide the first systematic review of animal models. We thoroughly searched all the studies involving rodents, profiling transcriptomic alterations consecutive to AD treatment in naïve animals or in animals subjected to stress-induced models of depression. We have been confronted by an important heterogeneity regarding the drugs and the experimental settings. Thus, we perform a meta-analysis of the AD signature of fluoxetine (FLX) in the hippocampus, the most studied target. Among genes and pathways consistently modulated across species, we identify both old players of AD action and novel transcriptional biomarker candidates that warrant further investigation. We discuss the most prominent transcripts (immediate early genes and activity-dependent synaptic plasticity pathways). We also stress the need for systematic studies of AD action in animal models that span across sex, peripheral and central tissues, and pharmacological classes.

Polyhydroxybutyrate (PHB) Scaffolds for Peripheral Nerve Regeneration: A Systematic Review of Animal Models.

Simple SummaryCurrently, polymeric biomaterials are the choice for the design of scaffolds for the regeneration of peripheral nerves. Polyhydroxybutyrate (PHB) is a polymer belonging to the class of polyesters that are produced naturally in nature by microorganisms. To gain a better understanding of the efficacy of therapeutic approaches involving PHB scaffolds for peripheral nerve regeneration, we conducted a systematic review of the literature with the aim of discussing the current knowledge of PHB scaffolds applied to nerve regeneration. The use of PHB as a biomaterial to prepare tubular scaffolds for nerve regeneration was shown to be promising. The incorporation of additives appears to be a trend that improves nerve regeneration.In the last two decades, artificial scaffolds for nerve regeneration have been produced using a variety of polymers. Polyhydroxybutyrate (PHB) is a natural polyester that can be easily processed and offer several advantages; hence, the purpose of this review is to provide a better understanding of the efficacy of therapeutic approaches involving PHB scaffolds in promoting peripheral nerve regeneration following nerve dissection in animal models. A systematic literature review was performed following the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) criteria. The revised databases were: Pub-Med/MEDLINE, Web of Science, Science Direct, EMBASE, and SCOPUS. Sixteen studies were included in this review. Different animal models and nerves were studied. Extension of nerve gaps reconnected by PHB scaffolds and the time periods of analysis were varied. The additives included in the scaffolds, if any, were growth factors, neurotrophins, other biopolymers, and neural progenitor cells. The analysis of the quality of the studies revealed good quality in general, with some aspects that could be improved. The analysis of the risk of bias revealed several weaknesses in all studies. The use of PHB as a biomaterial to prepare tubular scaffolds for nerve regeneration was shown to be promising. The incorporation of additives appears to be a trend that improves nerve regeneration. One of the main weaknesses of the reviewed articles was the lack of standardized experimentation on animals. It is recommended to follow the currently available guidelines to improve the design, avoid the risk of bias, maximize the quality of studies, and enhance translationality.

Efficacy of oral consumption of curcumin/ for symptom improvement in inflammatory bowel disease: A systematic review of animal models and a meta-analysis of randomized clinical trials

The roots of the vegetal Curcuma due to its high content of polyphenols, has been used successfully in several clinical situations. This review assessed the effect of curcumin/Curcuma longa on symptoms and metabolic changes in inflammatory bowel disease (IBD). A systematic review of animal models and randomized clinical trials (RCTs) was conducted by searching the following electronic databases: PubMed, CENTRAL, LILACS, Science Direct, and ClinicalTrials.gov. From 997 found records, 62 were included. More than 90% of the animal studies reported an improvement in macroscopic, histologic and/or functional activity; 80% identified decreased oxidative and/or inflammatory biomarkers in animals treated with curcumin. Among the RCTs, intention-to-treat analysis showed that oral curcumin was effective in inducing clinical remission (n = 281, RR: 3.15 CI 95% [1.22–8.10] p = 0.0017; i² = 72.2%, p = 0.006) and clinical response (n = 259, RR: 1.60 CI 95% [1.09–2.35] p = 0.0017; i² = 59.7%, p = 0.042) but not endoscopic remission (n = 161, RR: 2.91 CI 95% [0.58–14.58] p = 0.195; i² = 72.7%, p = 0.026). These results confirm that oral supplementation with curcumin/Curcuma longa has beneficial actions in animal colitis and, when associated with drug therapy, is effective in the treatment of patients with IBD.

A Systematic Review of Animal Models of Disuse-Induced Bone Loss.

Several different animal models are used to study disuse-induced bone loss. This systematic review aims to give a comprehensive overview of the animal models of disuse-induced bone loss and provide a detailed narrative synthesis of each unique animal model. PubMed and Embase were systematically searched for animal models of disuse from inception to November 30, 2019. In addition, Google Scholar and personal file archives were searched for relevant publications not indexed in PubMed or Embase. Two reviewers independently reviewed titles and abstracts for full-text inclusion. Data were extracted using a predefined extraction scheme to ensure standardization. 1964 titles and abstracts were screened of which 653 full-text articles were included. The most common animal species used to model disuse were rats (59%) and mice (30%). Males (53%) where used in the majority of the studies and genetically modified animals accounted for 7%. Twelve different methods to induce disuse were identified. The most frequently used methods were hindlimb unloading (44%), neurectomy (15%), bandages and orthoses (15%), and botulinum toxin (9%). The median time of disuse was 21days (quartiles: 14days, 36days) and the median number of animals per group subjected to disuse was 10 (quartiles: 7, 14). Random group allocation was reported in 43% of the studies. Fewer than 5% of the studies justified the number of animals per group by a sample size calculation to ensure adequate statistical power. Multiple animal models of disuse-induced bone loss exist, and several species of animals have successfully been studied. The complexity of disuse-induced bone loss warrants rigid research study designs. This systematic review emphasized the need for standardization of animal disuse research and reporting.

Animal models of disuse-induced bone loss: study protocol for a systematic review

BackgroundDisuse is a cardinal sign of various neurological diseases like stroke, cerebral palsy, and amyotrophic lateral sclerosis. Disuse leads to reduced mechanical loading of the skeleton, and a substantial and significant loss of bone mass quickly materializes. Several animal models have been proposed to investigate the pathogenesis of disuse-induced bone loss and to test new pharmaceutical targets to counteract it. As animal models may overcome several of the limitations in observational studies conducted in patients and allow for measurements not possible in humans, the primary objective of the present study is to provide a comprehensive overview of the available animal models of disuse-induced bone loss.Methods/designThis is a protocol for a systematic review of animal models of disuse-induced bone loss. An exhaustive search will be performed on PubMed and Embase in order to identify relevant studies. The primary outcome will be the method of disuse induction. The secondary outcomes will be related to bone samples and anatomical sites investigated, methods used to analyze and quantify bone loss, and bibliographic information. The protocol adheres to the current guiding principles of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) 2015 statement. Extracted data will be analyzed with descriptive statistics, and all the methods used to induce disuse will be described in detail with a narrative synthesis.DiscussionThis systematic review will provide an overview of available animal models of disuse-induced bone loss and discuss the different methods used to quantify and analyze the bone loss. Since bone loss caused by disuse is a hallmark of various diseases from different medical specialties, this overview will be of great benefit for all researchers planning to conduct disuse animal studies in the future.Systematic review registrationPROSPERO CRD42020157452.

A systematic review of animal models and sex as a variable in itch research

Introduction: Pruritus (or itch) research has gained momentum in the last decades and use of animal models to study itch behavior are a vital part of the research. Recent studies have found that many fields using animal models, including neuroscience, are predisposed toward using male animals in preclinical research. To address sex bias in animal research, the National Institutes of Health (NIH) began requiring researchers to include sex as a variable beginning in June 2015. Here, we test whether researchers studying itch are biased toward using males in preclinical research. Methods: The NIH’s PubMed database was searched for primary research articles written between August 2007 and December 2018 using the words “Itch” and “Pruritus.” The following information was extracted from articles fitting our inclusion criteria: type of itch (acute or chronic), the animal model and the sex of the animals used, and whether researchers considered sex as a variable. z-Tests, binomial tests, and the Cochran-Armitage test for trend were used to explore relationships between animal models and the usage of both sexes. Results: We found 5.3%±1.2% of papers in a given year used 1 of our 4 animal models. Mice were the most frequently used animal model, followed by rats, nonhuman primates, and dogs. Overall, researchers used male animals regardless of the animal model used. In preclinical research conducted on both male and female animals, sex was not considered a variable in a majority of these studies. Finally, since 2015, there has not been a change in the usage of male or female mice. Briefly, the incidence of papers utilizing both sexes has not changed. Discussion: We have found that itch researchers have a bias towards males in animal research. This bias has not changed since the NIH’s mandate to include sex as a variable in preclinical research.

Nonsteroidal Anti-Inflammatory Drugs and Their Neuroprotective Role After an Acute Spinal Cord Injury: A Systematic Review of Animal Models.

Study Design:Systematic review.Objective:Spinal cord injuries (SCIs) resulting in motor deficits can be devastating injuries resulting in millions of health care dollars spent per incident. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potential class of drugs that could improve motor function after an SCI. This systematic review utilizes PRISMA guidelines to evaluate the effectiveness of NSAIDs for SCI.Methods:PubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of “ibuprofen,” “meloxicam,” “naproxen,” “ketorolac,” “indomethacin,” “celecoxib,” “ATB-346,” “NSAID,” and “nonsteroidal anti-inflammatory drug” with “spinal.” Results were reviewed for relevance and included if they met inclusion criteria. The SYRCLE checklist was used to assess sources of bias.Results:A total of 2960 studies were identified in the PubMed/MEDLINE database using the above-mentioned search criteria. A total of 461 abstracts were reviewed in Scopus, 340 in CINAHL, 179 in PsycINFO, and 7632 in Embase. A total of 15 articles met the inclusion criteria.Conclusions:NSAIDs’ effectiveness after SCI is largely determined by its ability to inhibit Rho-A. NSAIDs are a promising therapeutic option in acute SCI patients because they appear to decrease cord edema and inflammation, increase axonal sprouting, and improve motor function with minimal side effects. Studies are limited by heterogeneity, small sample size, and the use of animal models, which might not replicate the therapeutic effects in humans. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries.

Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models.

It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.

Machine learning algorithms for systematic review: reducing workload in a preclinical review of animal studies and reducing human screening error

BackgroundHere, we outline a method of applying existing machine learning (ML) approaches to aid citation screening in an on-going broad and shallow systematic review of preclinical animal studies. The aim is to achieve a high-performing algorithm comparable to human screening that can reduce human resources required for carrying out this step of a systematic review.MethodsWe applied ML approaches to a broad systematic review of animal models of depression at the citation screening stage. We tested two independently developed ML approaches which used different classification models and feature sets. We recorded the performance of the ML approaches on an unseen validation set of papers using sensitivity, specificity and accuracy. We aimed to achieve 95% sensitivity and to maximise specificity. The classification model providing the most accurate predictions was applied to the remaining unseen records in the dataset and will be used in the next stage of the preclinical biomedical sciences systematic review. We used a cross-validation technique to assign ML inclusion likelihood scores to the human screened records, to identify potential errors made during the human screening process (error analysis).ResultsML approaches reached 98.7% sensitivity based on learning from a training set of 5749 records, with an inclusion prevalence of 13.2%. The highest level of specificity reached was 86%. Performance was assessed on an independent validation dataset. Human errors in the training and validation sets were successfully identified using the assigned inclusion likelihood from the ML model to highlight discrepancies. Training the ML algorithm on the corrected dataset improved the specificity of the algorithm without compromising sensitivity. Error analysis correction leads to a 3% improvement in sensitivity and specificity, which increases precision and accuracy of the ML algorithm.ConclusionsThis work has confirmed the performance and application of ML algorithms for screening in systematic reviews of preclinical animal studies. It has highlighted the novel use of ML algorithms to identify human error. This needs to be confirmed in other reviews with different inclusion prevalence levels, but represents a promising approach to integrating human decisions and automation in systematic review methodology.

Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence.

Fecal incontinence is a common disorder, but its pathophysiology is not completely understood. The aim of this review is to present animal models that have a place in the study of fecal incontinence. A literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in August 2016 revealed 50 articles of interest. Search terms included fecal/faecal incontinence and animal model or specific species. Articles not describing an animal model, in vitro studies, veterinary literature, reviews, and non-English articles were excluded. The articles described models in rats (n = 31), dogs (n = 8), rabbits (n = 7), and pigs (n = 4). Different fecal incontinence etiologies were modeled, including anal sphincter lesions (33 articles) ranging from a single anal sphincter cut to destruction of 50% of the anal sphincter by sharp dissection, electrocautery, or diathermy. Neuropathic fecal incontinence (12 articles) was achieved by complete or incomplete pudendal, pelvic, or inferior rectal nerve damage. Mixed fecal incontinence (5 articles) was modeled either by the inflation of pelvic balloons or an array of several lesions including nervous and muscular damage. Anal fistulas (2 articles), anal sphincter resection (3 articles), and diabetic neuropathy (2 articles) were studied to a lesser extent. Bias may have arisen from the authors' own work on fecal incontinence and the absence of blinding to the origins of articles. Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.

The Impact of Mean Arterial Pressure on Functional Outcome Post-Acute Spinal Cord Injury: A Scoping Systematic Review of Animal Models.

The aim of this work was to perform a scoping systematic review on the animal literature surrounding mean arterial blood pressure (MAP) and functional outcomes post-acute spinal cord injury (ASCI). We performed a systematic review of the literature by searching: MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to January 2015. We also performed a hand search of various published meeting proceedings. Through a two-step review process, using two independent reviewers, we selected articles for the final review based on pre-defined inclusion/exclusion criteria. Ten studies were included within the final systematic review. A variety of animal models were used within these studies. All included studies had some objective means of documenting functional outcome post-manipulation of the MAP. Four studies could be considered to be "positive studies," showing some neurological improvement or beneficial effect to having the blood pressure manipulated. Two studies displayed worse functional outcomes secondary to episodes of hypotension. Four studies failed to demonstrate a relationship between MAP and functional outcome within the animal models. This review concludes that, within the animal literature, there is insufficient evidence to draw a conclusion about the effect of MAP on neurological outcome in animal models of ASCI.

Vagus Nerve Stimulation for Treatment of Inflammation: Systematic Review of Animal Models and Clinical Studies

Vagus nerve stimulation (VNS) has been used since 1997 for treatment of drug-resistant epilepsy. More recently, an off-label use of VNS has been explored in animal models and clinical trials for treatment of a number of conditions involving the innate immune system. The underlying premise has been the notion of the cholinergic antiinflammatory pathway (CAP), mediated by the vagus nerves. While the macroanatomic substrate - the vagus nerve - is understood, the physiology of the pleiotropic VNS effects and the "language" of the vagus nerve, mediated brain-body communication, remain an enigma. Tackling this kind of enigma is precisely the challenge for and promise of bioelectronic medicine. We review the state of the art of this emerging field as it pertains to developing strategies for use of the endogenous CAP to treat inflammation and infection in various animal models and human clinical trials. This is a systematic PubMed review for the MeSH terms "vagus nerve stimulation AND inflammation." We report the diverse profile of currently used VNS antiinflammatory strategies in animal studies and human clinical trials. This review provides a foundation and calls for devising systematic and comparable VNS strategies in animal and human studies for treatment of inflammation. We discuss species-specific differences in the molecular genetics of cholinergic signaling as a framework to understand the divergence in VNS effects between species. Brain-mapping initiatives are needed to decode vagus-carried brain-body communication before hypothesis-driven treatment approaches can be devised.

Systematic review of animal models of middle ear surgery

Animal models of middle ear surgery help us to explore disease processes and intervention outcomes in a manner not possible in patients. This review begins with an overview of animal models of middle ear surgery which outlines the advantages and limitations of such models. Procedures of interest include myringoplasty/tympanoplasty, mastoidectomy, ossiculoplasty, stapedectomy, and active middle ear implants. The most important issue is how well the model reflects the human response to surgery. Primates are most similar to humans with respect to anatomy; however, such studies are uncommon now due to expense and ethical issues. Conversely, small animals are easily obtained and housed, but experimental findings may not accurately represent what happens in humans. We then present a systematic review of animal models of middle ear surgery. Particular attention is paid to any distinctive anatomical features of the middle ear, the method of accessing the REVIEW

Systematic review of animal models for the study of implant integration, assessing the influence of material, surface and design

The aim of this systematic review was to assess the scientific literature in terms of pre-clinical studies evaluating the influence of material, surface and design on the integration of an implant by hard and soft tissues. The included publications were analysed with regard to the frequency of reporting of criteria being derived from the ARRIVE guidelines. This served to trace elements within animal studies, where the quality of reporting needs to improve. The literature search was performed in Ovid Medline and included English literature from January 1990 to July 2011. A list of 24 criteria derived from the ARRIVE guidelines for animal research was adjusted to implant studies on osseointegration in pristine bone and was applied to all included study manuscripts. Each criteria was graded by "0" (not reported) or "1" (reported) and the frequency of reporting for each criteria was recorded. A total of 271 studies were included into this review. Generally the quality of reporting increased with time. Low frequencies of reporting were achieved for criteria like "randomisation of animals", "reasons for the animal model" and "relevance to humans". The frequency of reporting showed high percentages for most criteria. However, the quality of reporting in pre-clinical studies needs to improve in areas like the reporting of statistical information, study setup and the possible translation of the results to humans.

Systematic review of animal models of post-infectious/post-inflammatory irritable bowel syndrome

Post-infectious irritable bowel syndrome (PI-IBS) is a subset of IBS which occurs after an episode of acute gastrointestinal infections. The mechanisms of PI-IBS are not fully understood. Currently, numerous animal models have been used in the study of PI-IBS. This article reviews the strengths and weaknesses of these models. All relevant articles were identified by searching in Ovid SP from 1962, the year the term PI-IBS was coined, up to December 31, 2009. The types of model were categorized as either post-infectious or post-inflammatory, and the characteristics of each kind of model were listed. Based on our literature search, 268 articles were identified. Of those articles, 50 were included in this review. The existing PI-IBS models include infection with bacteria (e.g., Campylobacter jejuni, Salmonella enterica, and Campylobacter rodentium), and infection with parasites (e.g., Trichinella spiralis, Nippostrongylus brasiliensis, and Cryptosporidium parvum). The post-inflammatory IBS models are commonly induced with chemical agents, such as acetic acid, deoxycholic acid, dextran sulfate sodium, mustard oil, zymosan, and trinitrobenzene sulfonic acid (TNBS). TNBS is the most commonly used agent for post-inflammatory IBS models, but the experimental protocol varies. These models have one or more aspects similar to IBS patients. Different methods have been used for the development of post-infectious or post-inflammatory IBS models. Each model has its weaknesses and strengths. More studies are needed to establish post-infection IBS models using more common pathogens. A standard protocol in developing TNBS-induced post-inflammatory IBS model is needed.

A systematic review on animal models of maternal high fat feeding and offspring glycaemic control

The mechanistic link between obese parents and obese offspring and the relative role of genes, and a shared environment is not completely understood. Animal models help us to differentiate between genetic and environmental factors, and the interaction between the two. However, the willingness of researchers to blend results from multiple models makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we conducted a systematic review of animal models of maternal high fat feeding in an effort to identify the affect on the offspring glycaemic control. Maternal and offspring outcomes are reported in an effort to identify possible relationships to facilitate and focus on future research. We present here data from 11 studies investigating glycaemic control in offspring exposed to a high fat diet (HFD) during maternal gestation only or gestation and lactation. Studies in this review identify a real risk of type 2 diabetes and obesity in male offspring exposed to a maternal HFD. Poor glycaemic control in the offspring appears to be independent of maternal obesity, birth weight or post-weaning macronutrient intake. Inconsistencies between studies however, limit our capacity to identify mechanisms for the developmental origin of these diseases in animal models of overnutrition.

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. Pathologically, three lesions are seen: small vessel arteriopathy, lacunar infarction, and diffuse white matter injury (leukoaraiosis). Appropriate experimental models would aid in understanding these pathologic states and also in preclinical testing of therapies. The objective was to perform a systematic review of animal models of SVD and determine whether these resemble four key clinicopathologic features: (1) small, discrete infarcts; (2) small vessel arteriopathy; (3) diffuse white matter damage; (4) cognitive impairment. Fifteen different models were included, under four categories: (1) embolic injuries (injected blood clot, photochemical, detergent-evoked); (2) hypoperfusion/ischaemic injury (bilateral common carotid occlusion/stenosis, striatal endothelin-1 injection, striatal mitotoxin 3-NPA); (3) hypertension-based injuries (surgical narrowing of the aorta, or genetic mutations, usually in the renin-angiotensin system); (4) blood vessel damage (injected proteases, endothelium-targeting viral infection, or genetic mutations affecting vessel walls). Chronic hypertensive models resembled most key features of SVD, and shared the major risk factors of hypertension and age with human SVD. The most-used model was the stroke-prone spontaneously hypertensive rat (SHR-SP). No model described all features of the human disease. The optimal choice of model depends on the aspect of pathophysiology being studied.