Objectives
To assess the recovery of urinary continence, faecal continence and tail function in ambulatory dogs with caudal lumbar intervertebral disc extrusion and to explore clinical factors that ...may be associated with recovery.
Materials and Methods
Medical records from January 2010 to December 2020 were searched to identify ambulatory dogs undergoing surgical treatment for a caudal lumbar intervertebral disc extrusion causing urinary incontinence, faecal incontinence and/or tail dysfunction. Signalment, history, presenting clinical signs, neurological examination findings, diagnostic test results, treatment and outcome were recorded for all dogs.
Results
Eighteen dogs with caudal lumbar intervertebral disc extrusion causing tail dysfunction, urinary and/or faecal incontinence were included. Urinary continence was recovered in 12 (86%) of 14 affected dogs, faecal continence recovered in nine (90%) of 10 affected dogs and tail function recovered in 13 (87%) of 15 affected dogs. Loss of tail nociception was recorded in three dogs on presentation; two made a full recovery and one showed mild persistent tail paresis.
Clinical Significance
The prognosis for functional recovery of urinary continence, faecal continence and tail function in ambulatory dogs with caudal lumbar intervertebral disc extrusion following surgical treatment is good. Larger studies are needed to identify prognostic factors associated with failure of recovery.
Faculty in the health professions need to demonstrate teaching effectiveness and faculty development of teaching can help them achieve this expectation. While there are several development options, ...the utility of an Education Grand Rounds was explored. The objectives were to coordinate eight yearly sessions focused on six topic priorities, involve our main and distant campus and national presenters, deliver live sessions to the main and distant campus and video-capture sessions, and dedicate session time to active learning. Education Grand Rounds was developed by faculty and administrative representatives from all six colleges on our two campuses and made available to all faculty at our academic health sciences center. Six sessions topics were prioritized: didactic and clinical teaching, education research, assessment/evaluation, education administration, and instructional technology. Over five years, eight active learning sessions a year were delivered to the main and distant campuses emphasizing six prioritized teaching areas, included local and national presenters, with sixteen sessions video-captured. On average monthly attendance was nineteen from the main and three from the distant campuses, representing five of six disciplines. The majority of attendees reported above/significantly above average satisfaction with the sessions. Education Grand Rounds is a sustainable form of faculty development for health sciences center faculty located on two campuses. Future directions should assess the impact of topic sequencing presented in multiple modalities, synchronous versus asynchronous participation, and the types of active learning used on participants' teaching improvement and change as a result of the sessions.
This study examined department chairs’ perceptions about the importance of an interprofessional mentor and the completion of a Scholarship in Progress (SiP) pilot research study for early career ...faculty (ECF) in an 11-month Faculty Leadership Program (FLP) at an Academic Health Center (AHC).
FLP is a faculty development program for ECF that includes a series of workshops focused on teaching, research/scholarship, and service/leadership skills and roles needed within the AHC environment. FLP participants are required to complete a research pilot project with the help of a research mentor.
A 21-question, web-based survey instrument was developed to assess the value of FLP’s research mentorship and project and was administered to 53 department chairs across the 6 AHC colleges who had FLP participants graduate during 2008 to 2013.
A total of 24 out of 53 (45%) of the department chairs completed the study questionnaire representing 5 of the 6 colleges. Of those responders, 61% reported that having research mentors, such as biostatisticians and 80% reported that having pilot research projects for ECF were important for faculty success at the AHC.
This requirement is important as department chairs report the importance of research mentors, such as biostatisticians and having pilot research projects for faculty success at the AHC.
ECVAM sponsored a formal validation study on three in vitro tests for skin irritation, of which two employ reconstituted human epidermis models (EPISKIN, EpiDerm), and one, the skin integrity ...function test (SIFT), employs ex vivo mouse skin. The goal of the study was to assess whether the in vitro tests would correctly predict in vivo classifications according to the EU classification scheme, "R38" and "no label" (i.e. non-irritant). 58 chemicals (25 irritants and 33 non-irritants) were tested, having been selected to give broad coverage of physico-chemical properties, and an adequate distribution of irritancy scores derived from in vivo rabbit skin irritation tests. In Phase 1, 20 of these chemicals (9 irritants and 11 non-irritants) were tested with coded identities by a single lead laboratory for each of the methods, to confirm the suitability of the protocol improvements introduced after a prevalidation phase. When cell viability (evaluated by the MTT reduction test) was used as the endpoint, the predictive ability of both EpiDerm and EPISKIN was considered sufficient to justify their progression to Phase 2, while the predictive ability of the SIFT was judged to be inadequate. Since both the reconstituted skin models provided false predictions around the in vivo classification border (a rabbit Draize test score of 2), the release of a cytokine, interleukin-1α (IL-1α), was also determined. In Phase 2, each human skin model was tested in three laboratories, with 58 chemicals. The main endpoint measured for both EpiDerm and EPISKIN was cell viability. In samples from chemicals which gave MTT assay results above the threshold of 50% viability, IL-1α release was also measured, to determine whether the additional endpoint would improve the predictive ability of the tests. For EPISKIN, the sensitivity was 75% and the specificity was 81% (MTT assay only); with the combination of the MTT and IL-1α assays, the sensitivity increased to 91%, with a specificity of 79%. For EpiDerm, the sensitivity was 57% and the specificity was 85% (MTT assay only), while the predictive capacity of EpiDerm was not improved by the measurement of IL-1α release. Following independent peer review, in April 2007 the ECVAM Scientific Advisory Committee endorsed the scientific validity of the EPISKIN test as a replacement for the rabbit skin irritation method, and of the EpiDerm method for identifying skin irritants as part of a tiered testing strategy. This new alternative approach will probably be the first use of in vitro toxicity testing to replace the Draize rabbit skin irritation test in Europe and internationally, since, in the very near future, new EU and OECD Test Guidelines will be proposed for regulatory acceptance.
Objective
Messenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome‐wide ...posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes.
Methods
Human articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels in samples were confirmed using quantitative reverse transcription–polymerase chain reaction.
Results
Examination of total mRNA expression levels demonstrated significant differences in the expression of transcripts between normal and OA chondrocytes. Interestingly, almost no difference was observed in total mRNA expression between chondrocytes from intact OA cartilage and those from fibrillated OA cartilage. Decay analysis revealed a set of rapidly turned over transcripts associated with transcriptional control and programmed cell death that were common to all chondrocytes and contained binding sites for abundant cartilage microRNAs. Many transcripts exhibited altered mRNA half‐lives in human OA chondrocytes compared to normal cells. Specific transcripts whose decay rates were altered were generally less stable in these pathologic cells. Examination of selected genes in chondrocytes from young and old healthy horses did not identify any change in mRNA turnover.
Conclusion
This is the first investigation into the “posttranscriptome” of the chondrocyte. It identifies a set of short‐lived chondrocyte mRNAs likely to be highly responsive to altered transcriptional input as well as mRNAs whose decay rates are affected in OA chondrocytes.
The Processing of Positive Memories Technique (PPMT) is a promising new treatment approach for posttraumatic stress disorder (PTSD), which involves detailed narration and processing of specific ...positive autobiographical memories. Indeed, preliminary case-series studies have found reductions in PTSD symptoms, negative affect, and negative cognitions among survivors of trauma who have received PPMT. However, PPMT's effects have not been investigated at the daily level. In this study, we describe the protocol for a study that will examine the daily-level impacts of PPMT in a trauma-exposed, nonclinical community sample.
This study uses an innovative research protocol that combines case-series design and daily diary approaches to examine changes in daily affect, daily cognitions, and daily PTSD symptoms pre- and post-PPMT. We hypothesize that at the daily level, in comparison to their own pre-PPMT levels, following the PPMT intervention, participants will report (1) a lower count of endorsed daily PTSD symptoms, (2) increases in daily positive affect and decreases in daily negative affect, (3) increases in positive affect reactivity to daily positive events, and (4) decreases in daily posttrauma cognitions.
We are currently recruiting participants (target n=70) from a metroplex in the southwest United States. Following a screening survey, eligible participants complete a preintervention baseline survey, followed by 21 daily surveys in their natural environments. Then, they receive 4 PPMT sessions on a weekly basis. After the conclusion of the PPMT intervention, participants complete a postintervention outcome survey and 21 daily surveys. To compare daily affect, daily cognitions, and daily PTSD symptoms before and after PPMT, we will use the daily diary report data and conduct multilevel random intercepts and slopes linear regression models.
Data collection was initiated in March 2022 and is expected to end by June 2024. As of November 28, 2023, a total of 515 participants had consented to the study in the screening phase. No analyses will be conducted until data collection has been completed.
Study findings could clarify whether deficits in positive autobiographical memory processes may also characterize PTSD alongside deficits in traumatic memory processes. Furthermore, PPMT could be an additional therapeutic tool for clinicians to help clients reduce posttraumatic distress in their everyday lives.
DERR1-10.2196/51838.
As a follow-up to a prevalidation study on
in vitro tests for replacing the
in vivo rabbit test for skin corrosivity, an international validation study was conducted during 1996 and 1997 under the ...auspices of ECVAM. The main objectives of the study were to: (a) identify tests capable of discriminating corrosives from non-corrosives for selected types of chemicals and/or all chemicals; and (b) determine whether these tests could identify correctly known R35 (UN packing group I) and R34 (UN packing groups II & III) chemicals. The tests evaluated were the rat skin transcutaneous electrical resistance (TER) assay, CORROSITEX
TM, the S
kin
2TM ZK1350 corrosivity test and EPISKIN
TM. Each test was conducted in three independent laboratories. 60 coded chemicals were tested. All of the tests evaluated showed acceptable intralaboratory and interlaboratory reproducibilities, and the TER, Skin
2 and EPISKIN tests proved applicable to testing a diverse group of chemicals of different physical forms, including organic acids, organic bases, neutral organics, inorganic acids, inorganic bases, inorganic salts, electrophiles, phenols and soaps/surfactants. Two of the four tests evaluated, the TER assay and EPISKIN, met the criteria agreed by the Management Team concerning acceptable underprediction and overprediction rates for them to be considered scientifically validated for use as replacements for the animal test for distinguishing between corrosive and non-corrosive chemicals for all of the chemical types studied objective (a). EPISKIN was the only test able to distinguish between known R35 (UN packing group I) and R34 (UN packing groups II & III) chemicals, for all of the chemical types included, on an acceptable number of occasions objective (b). The corrosive potentials of about 40% of the test chemicals could not be assessed with CORROSITEX, and the assay did not meet all of the criteria for it to be considered acceptable as a replacement test. However, CORROSITEX may be valid for testing specific classes of chemicals, such as organic bases and inorganic acids. The Skin
2 assay did not meet the criteria for it to be considered scientifically validated. Thus, the validities of (i) the TER and EPISKIN assays for discriminating corrosives from non-corrosives, and (ii) the EPISKIN assay for identifying correctly known R35/I and R34/II & III chemicals, have been demonstrated in this study. CORROSITEX appears to be valid when used only with certain types of chemicals.
A prevalidation study on in vitro tests for acute skin irritation was conducted during 1999 and 2000. The overall objective of validation in this area, of which this prevalidation study is an initial ...stage, is to identify tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union (EU) risk phrases (“R38”; no classification) and the harmonised OECD criteria (“Irritant”; no label). This prevalidation study specifically addressed aspects of: protocol refinement (phase I), protocol transfer (phase II), and protocol performance (phase III), in accordance with the prevalidation scheme defined by the European Centre for the Validation of Alternative Methods (ECVAM). The tests evaluated were: EpiDerm™ (phases I, II and III), EPISKIN™ (phases I, II and III), PREDISKIN™ (phases I and II, and additional protocol refinement), the non-perfused pig ear method (phases I and II, and additional protocol refinement), and the mouse skin integrity function test (SIFT; phases I and II). Modified, standardised test protocols and well-defined prediction models were available for each of the tests at the end of phase I. The results of phase I (intralaboratory reproducibility) were sufficiently promising for all of the tests to progress to phase II. Protocol transfer between the Lead Laboratory and Laboratory 2 was undertaken for all five tests during phase II, and additional refinements were made to the test protocols. For EpiDerm, EPISKIN and the SIFT, the intralaboratory and interlaboratory reproducibilities were acceptable; however, better standardisation of certain aspects of the test protocols was needed prior to commencing phase III. Neither PREDISKIN nor the pig ear test performed sufficiently well in phase II to progress to phase III. The PREDISKIN protocol was overly sensitive, resulting in the prediction of all the NI chemicals as I. The variability in the pig ear test results was too great, indicating that the test would show limited predictive ability. In additional studies (a repeat of phase I), further modification of the PREDISKIN protocol and a change in the prediction model considerably improved the ability of the test to distinguish I from NI chemicals. However, attempts to improve the intralaboratory reproducibility of the pig ear test were unsuccessful. In phase III an initial assessment of the reproducibility and predictive ability, in three independent laboratories per test, was undertaken for the EpiDerm and EPISKIN tests (the SIFT was a late inclusion in the prevalidation study, and is being evaluated in a separate phase III study). A set of 20 coded chemicals (10 I, 10 NI) were tested with the final, refined, test protocols. The intralaboratory reproducibility was acceptable for both EpiDerm and EPISKIN. The interlaboratory reproducibility was considered to be acceptable for EPISKIN; however, for EpiDerm, analysis of variance (ANOVA) indicated that there was a statistically significant laboratory effect on the overall variability, suggesting that the interlaboratory transferability of the test needs to be improved. The EpiDerm test had an overall accuracy of 58%, with an over-prediction rate of 37% and an under-prediction rate of 47%. The EPISKIN test had an overall accuracy of 58%, showing an under-prediction rate of 23% and an over-prediction rate of 60%. It is concluded that, as yet, none of the tests evaluated in this prevalidation study are ready for inclusion in a formal validation study on in vitro tests for acute skin irritation. Overall protocol performance of the SIFT is currently being evaluated in a phase III study. Further studies are also in progress to improve the test protocols and prediction models for EpiDerm and EPISKIN.
Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This ...understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved.
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