-
Perspectives on Behavior Science Mar 2023Resurgence is the return of a previously reinforced response as conditions worsen for an alternative response, such as the introduction of extinction, reductions in... (Review)
Review
UNLABELLED
Resurgence is the return of a previously reinforced response as conditions worsen for an alternative response, such as the introduction of extinction, reductions in reinforcement, or punishment. As a procedure, resurgence has been used to model behavioral treatments and understand behavioral processes contributing both to relapse of problem behavior and flexibility during problem-solving. Identifying existing procedural and analytic methods arranged in basic/preclinical research could be used by basic and preclinical researchers to develop novel approaches to study resurgence, whereas translational and clinical researchers could identify potential approaches to combating relapse during behavioral interventions. Despite the study of resurgence for over half a century, there have been no systematic reviews of the basic/preclinical research on resurgence. To characterize the procedural and analytic methods used in basic/preclinical research on resurgence, we performed a systematic review consistent with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We identified 120 articles consisting of 200 experiments that presented novel empirical research, examined operant behavior, and included standard elements of a resurgence procedure. We reported prevalence and trends in over 60 categories, including participant characteristics (e.g., species, sample size, disability), designs (e.g., single subject, group), procedural characteristics (e.g., responses, reinforcer types, control conditions), criteria defining resurgence (e.g., single test, multiple tests, relative to control), and analytic strategies (e.g., inferential statistics, quantitative analysis, visual inspection). We make some recommendations for future basic, preclinical, and clinical research based on our findings of this expanding literature.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40614-022-00361-y.
PubMed: 37006602
DOI: 10.1007/s40614-022-00361-y -
Medical Education Online 2015Preclinical medical student electives are prevalent at medical schools across the United States, but the range of electives available and their impact on medical student... (Review)
Review
OBJECTIVE
Preclinical medical student electives are prevalent at medical schools across the United States, but the range of electives available and their impact on medical student education are not well described in the literature. The objective of this article is to review the literature relating to preclinical medical student electives and their impact on medical student educational outcomes.
METHODS
We reviewed studies that met the following criteria: English-language articles describing preclinical US-based medical electives. We used PubMed journal databases and limited our search for the time period 1999-2014. We excluded electives based in other countries or electives designed for third or fourth year students. Data abstracted included the topic of the elective, qualitative descriptions of the electives, and any associated surveys or exam data associated with the electives. Data were synthesized using descriptive tables sorting electives by broad topic. Reported outcomes and statistical methods were analyzed to assess study quality.
RESULTS
We found a wide range of subjects taught in the form of preclinical medical school electives. We identified electives in clinical skills, the humanities, student lifestyle, specialty-specific electives, and an assortment of other miscellaneous electives. Surveys and exams administered to students showed that the electives were universally well received by students. Of the 37 electives identified, 15 electives used quantitative objective assessments, such as knowledge exams, while the remaining tended to use student self-reported results.
CONCLUSIONS
Preclinical medical student electives are prevalent at medical schools across the United States and have a significant impact on medical student education.
Topics: Clinical Competence; Curriculum; Education, Medical, Undergraduate; Educational Measurement; Humans; Life Style; Medicine; Perception; United States
PubMed: 25968131
DOI: 10.3402/meo.v20.26615 -
Clinical and Translational Radiation... Jul 2022Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an... (Review)
Review
Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.
PubMed: 35601799
DOI: 10.1016/j.ctro.2022.04.013 -
Paediatric Anaesthesia Jan 2016Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings... (Review)
Review
A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research.
UNLABELLED
Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing human brain.
AIM
The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials.
METHOD
The literature search identified 941 articles related to the topic of neurotoxicity. As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of neurotoxicity and the neuroprotective agents. Forty-seven preclinical studies were finally included in this review.
RESULTS
Methods used in these studies were highly heterogeneous-animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse toxicity profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to humans.
CONCLUSION
Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to humans remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science.
Topics: Anesthetics; Animals; Animals, Newborn; Brain; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Haplorhini; Mice; Neuroprotective Agents; Neurotoxicity Syndromes; Rats
PubMed: 26530523
DOI: 10.1111/pan.12786 -
The Journal of Pain Jun 2023This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behavior and biomarkers in preclinical models of... (Meta-Analysis)
Meta-Analysis Review
This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behavior and biomarkers in preclinical models of focal neuropathic pain. We searched MEDLINE, EMBASE, Web of Science, PubMed, SCOPUS, CINAHL, and Cochrane library from inception to November 2022 for preclinical studies evaluating the effect of exercise compared to control interventions on neuropathic pain behavior after experimental sciatic nerve injury. If possible, data were meta-analyzed using random effect models with inverse-variance weighting. Thirty-seven studies were included and 26 meta-analyzed. Risk of bias (SYRCLE tool) remained unclear in most studies and reporting quality (CAMARADES) was variable. Exercise reduced mechanical (standardized mean differences [SMD] .53 (95% CI .31, .74), P = .0001, I = 0%, n = 364), heat (.32 (.07, .57), P = .01, I = 0%, n = 266) and cold hypersensitivity (.51 (.03, 1.0), P = .04, I = 0%, n = 90) compared to control interventions. No relationship was apparent between exercise duration or intensity and antinociception. Exercise modulated biomarkers related to different systems (eg, immune system, neurotrophins). Whereas firm conclusions are prevented by the use of male animals only, variable reporting quality and unclear risk of bias in many studies, our results suggest that aerobic exercise is a promising tool in the management of focal neuropathic pain. PERSPECTIVE: This systematic review and meta-analysis demonstrates that aerobic exercise reduces neuropathic pain-related behavior in preclinical models of sciatic nerve injury. This effect is accompanied by changes in biomarkers associated with inflammation and neurotrophins among others. These results could help to develop exercise interventions for patients with neuropathic pain.
Topics: Animals; Male; Exercise; Neuralgia; Sciatic Nerve
PubMed: 36690283
DOI: 10.1016/j.jpain.2023.01.011 -
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693 -
Global Spine Journal Apr 2020Systematic review. (Review)
Review
The Impact of Riluzole on Neurobehavioral Outcomes in Preclinical Models of Traumatic and Nontraumatic Spinal Cord Injury: Results From a Systematic Review of the Literature.
STUDY DESIGN
Systematic review.
OBJECTIVE
To evaluate the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI).
METHODS
An extensive search of the literature was conducted in Medline, EMBASE, and Medline in Process. Studies were included if they evaluated the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI. Extensive data were extracted from relevant studies, including sample characteristics, injury model, outcomes assessed, timing of evaluation, and main results. The SYRCLE checklist was used to assess various sources of bias.
RESULTS
The search yielded a total of 3180 unique citations. A total of 16 studies were deemed relevant and were summarized in this review. Sample sizes ranged from 14 to 90, and injury models included traumatic SCI (n = 9), degenerative cervical myelopathy (n = 2), and spinal cord-ischemia (n = 5). The most commonly assessed outcome measures were BBB (Basso, Beattie, Besnahan) locomotor score and von Frey filament testing. In general, rats treated with riluzole exhibited significantly higher BBB locomotor scores than controls. Furthermore, riluzole significantly increased withdrawal thresholds to innocuous stimuli and tail flick latency following application of radiant heat stimuli. Finally, rats treated with riluzole achieved superior results on many components of gait assessment.
CONCLUSION
In preclinical models of traumatic and nontraumatic SCI, riluzole significantly improves locomotor scores, gait function, and neuropathic pain. This review provides the background information necessary to interpret the results of clinical trials on the impact of riluzole in traumatic and nontraumatic SCI.
PubMed: 32206521
DOI: 10.1177/2192568219835516 -
PLoS Medicine 2013The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is... (Review)
Review
BACKGROUND
The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address.
METHODS AND FINDINGS
We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.
CONCLUSIONS
By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.
Topics: Animal Experimentation; Animals; Drug Evaluation, Preclinical; Guidelines as Topic; Humans; Research Design
PubMed: 23935460
DOI: 10.1371/journal.pmed.1001489 -
Neuroscience and Biobehavioral Reviews Dec 2021The oxytocin (OXT) system has garnered considerable interest due to its influence on diverse behaviours. However, scant research has considered the influence of oxytocin... (Review)
Review
The oxytocin (OXT) system has garnered considerable interest due to its influence on diverse behaviours. However, scant research has considered the influence of oxytocin on sleep-wake and sleep-related behaviour and neurobiology. Consequently, the objective of this systematic review was to assess the extant preclinical and clinical evidence for the influence of oxytocin-based interventions on sleep-wake outcomes. The primary search was conducted on 22/7/2020 using six electronic databases; 30 studies (19 preclinical, 11 clinical) were included based on inclusion criteria. Studies were evaluated for risk of bias using the SYRCLE tool and the Cochrane risk of bias tools for preclinical and clinical studies, respectively. Results indicated manipulation of the OXT system can influence sleep-wake outcomes. Preclinical evidence suggests a wake-promoting influence of OXT system activation whereas the clinical evidence suggests little or no sleep-promoting influence of OXT. OXT dose was identified as a likely modulatory factor of OXT-induced effects on sleep-wake behaviour. Future studies are necessary to validate and strengthen these tentative conclusions about the influence of OXT on sleep-wake behaviour.
Topics: Humans; Neurobiology; Oxytocin; Sleep
PubMed: 34673110
DOI: 10.1016/j.neubiorev.2021.10.016 -
Cancers Dec 2019Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast... (Review)
Review
Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up- and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.
PubMed: 31847214
DOI: 10.3390/cancers11122018