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A Working Group of the Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee conducted a technical and scientific review of current practices relating to the fixation, trimming, and sectioning of the nonrodent eye to identify key points and species-specific anatomical landmarks to consider when preparing and evaluating eyes of rabbits, dogs, minipigs, and nonhuman primates from ocular and general toxicity studies. The topics addressed in this Points to Consider article include determination of situations when more comprehensive evaluation of the globe and/or associated extraocular tissues should be implemented (expanded ocular sampling), and what constitutes expanded ocular sampling. In addition, this manuscript highlights the practical aspects of fixing, trimming, and sectioning the eye to ensure adequate histopathological evaluation of all major ocular structures, including the cone-dense areas (visual streak/macula/fovea) of the retina for rabbits, dogs, minipigs, and nonhuman primates, which is a current regulatory expectation for ocular toxicity studies.[Box: see text].

Background. Due to an increasing stroke incidence, a lack of resources to implement effective rehabilitation and a significant proportion of patients with remaining impairments after treatment, there is a rise in demand for effective and prolonged rehabilitation. Development of self-rehabilitation programs provides an opportunity to meet these increasing demands. Objective. The primary aim of this meta-analysis was to determine the effect of self-rehabilitation on motor outcomes, in comparison to conventional rehabilitation, among patients with stroke. The secondary aim was to assess the influence of trial location (continent), technology, time since stroke (acute/subacute vs chronic), dose (total training duration > vs ≤ 15 hours), and intervention design (self-rehabilitation in addition/substitution to conventional therapy) on effect of self-rehabilitation. Methods. Studies were selected if participants were adults with stroke; the intervention consisted of a self-rehabilitation program defined as a tailored program where for most of the time, the patient performed rehabilitation exercises independently; the control group received conventional therapy; outcomes included motor function and activity; and the study was a randomized controlled trial with a PEDro score ≥5. Results. Thirty-five trials were selected (2225 participants) and included in quantitative synthesis regarding motor outcomes. Trials had a median PEDro Score of 7 [6-8]. Self-rehabilitation programs were shown to be as effective as conventional therapy. Trial location, use of technology, stroke stage, and intervention design did not appear to have a significant influence on outcomes. Conclusion. This meta-analysis showed low to moderate evidence that self-rehabilitation and conventional therapy efficacy was equally valuable for post-stroke motor function and activity.

The Society of Toxicologic Pathology (STP, https://www.toxpath.org/) was founded in North America in 1971 as a nonprofit scientific and educational association to promote the professional practice of pathology as applied to pharmaceutical and environmental safety assessment. In the ensuing 50 years, the STP has become a principal global leader in the field. Society membership has expanded to include toxicologic pathologists and allied scientists (eg, toxicologists, regulatory reviewers) from many nations. In addition to serving membership needs for professional development and networking, major STP outreach activities include production of articles and presentations designed to optimize toxicologic pathology procedures ("best practice" recommendations), communicate core principles of pathology evaluation and interpretation ("points to consider" and "opinion" pieces), and participation in international efforts to harmonize diagnostic nomenclature. The STP has evolved into an essential resource for academic, government, and industrial organizations that employ and educate toxicologic pathologists as well as use toxicologic pathology data across a range of applications from assessing product safety (therapies, foods, etc) to monitoring and maintaining environmental and occupational health. This article recapitulates the important milestones and accomplishments of the STP during its first 50 years.

In a juvenile toxicology program, an unexpected finding of vacuolation of inner nuclear, ganglion cell, and nerve fiber layers of the retina was observed microscopically in routine Davidson's fixed and hematoxylin and eosin-stained tissue sections of eyes in beagle dogs at approximately 5 weeks of age. There was no necrosis or degeneration of the affected cells and no associated inflammation. Fluorescein angiography revealed no vascular leakage. Optical coherence tomography (OCT) indicated swollen cells in the same layers of the retina as observed at light microscopic examination. Transmission electron microscopy revealed that the retinal vacuolation likely was consistent with intracellular swelling of amacrine, horizontal, and/or bipolar cells of the inner nuclear layer as affected cells had an expanded cytoplasm but contained normal nucleus and organelles. As assessed by animal behavior and full-field electroretinography, the retinal vacuolation appeared to have no impact on visual function. Retinal vacuolation was seen in approximately 40% of dogs at 5 weeks of age using OCT and/or light microscopic examination. Because the change was transient and age related, did not result in degenerative retinal changes, and was not present in dogs older than 5 weeks of age, it was considered a background developmental observation in beagle dogs.

Spontaneous findings noted in the eyes of Mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. Findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. Also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most of which a standard histopathological examination of 1 section per eye was conducted. Common observations in monkeys examined extensively and in historical controls were limited to lymphocytic or mononuclear cell infiltrations of the uvea and/or conjunctiva/sclera and, less commonly observed, melanocytoma of the ciliary body or iris. Findings noted only in monkeys examined extensively consisted of inflammation of the conjunctiva, ora serrata cysts, glial nodules, focal degeneration of the retina, cystoid degeneration of the central retina, ballooning degeneration of the ciliary epithelium, cyst of the ciliary body, and decreased pigmentation of the retinal pigment epithelium. Changes recorded only in historical controls included retinal atrophy and nuclear displacement in the retina. Lesions are discussed and compared with pertinent literature.

Background: Selective neurotomy is a permanent treatment of focal spasticity, and its effectiveness in treating spastic equinovarus of the foot (SEF) was previously suggested by a few nonrandomized and uncontrolled case-series studies., Objectives: This study is the first assessor-blinded, randomized, controlled trial evaluating the effects of this treatment., Methods: Sixteen chronic stroke patients presenting with SEF were randomized into 2 groups: 8 patients underwent a tibial neurotomy and the remaining 8 received botulinum toxin (BTX) injections. The soleus was treated in all patients, and the tibialis posterior and flexor hallucis longus were treated in about half of patients. The primary outcome was the quantitative measurement of ankle stiffness (L-path), an objective measurement directly related to spasticity. Participants were assessed by a blind assessor before their intervention and at 2 and 6 months after treatment. Evaluations were based on the 3 domains of the International Classification of Functioning, Disability and Health (ICF)., Results: Compared with BTX, tibial neurotomy induced a higher reduction in ankle stiffness. Both treatments induced a comparable improvement of ankle kinematics during gait, whereas neither induced muscle weakening. Activity, participation, and quality of life were not significantly modified in either group., Conclusions: This study demonstrates that the tibial nerve neurotomy is an effective treatment of SEF, reducing the impairments observed in chronic stroke patients. Future studies should be conducted to confirm the long-term efficacy based on the ICF domains.