Hydrogels derived from decellularized lungs are promising materials for tissue engineering in the development of clinical therapies and for modeling the lung extracellular matrix (ECM)
. ...Characterizing and controlling the resulting physical, biochemical, mechanical, and biologic properties of decellularized ECM (dECM) after enzymatic solubilization and gelation are thus of key interest. As the role of enzymatic pepsin digestion in effecting these properties has been understudied, we investigated the digestion time-dependency on key parameters of the resulting ECM hydrogel. Using resolubilized, homogenized decellularized pig lung dECM as a model system, significant time-dependent changes in protein concentration, turbidity, and gelation potential were found to occur between the 4 and 24 h digestion time points, and plateauing with longer digestion times. These results correlated with qualitative scanning electron microscopy images and quantitative analysis of hydrogel interconnectivity and average fiber diameter. Interestingly, the time-dependent changes in the storage modulus tracked with the hydrogel interconnectivity results, while the Young's modulus values were more closely related to average fiber size at each time point. The structural and biochemical alterations correlated with significant changes in metabolic activity of several representative lung cells seeded onto the hydrogels with progressive decreases in cell viability and alterations in morphology observed in cells cultured on hydrogels produced with dECM digested for >12 and up to 72 h of digestion. These studies demonstrate that 12 h pepsin digest of pig lung dECM provides an optimal balance between desirable physical ECM hydrogel properties and effects on lung cell behaviors.
Athletic trainers (ATs) must be equipped with evidence to inform their clinical practice. A systematic, inclusive, and continuous process for exploring research priorities is vital to the success of ...ATs and, more importantly, their patients' positive outcomes.
To identify research priorities and unify research with clinical practice to improve patient care and advance the profession.
Mixed-methods study.
Focus groups and a Web-based survey.
A total of 87 ATs (43 men 49.4%, 44 women 50.6%; age = 40 ± 11 years; experience = 18 ± 11 years) participated in focus groups. Of the 49 332 e-mails sent, 580 were undeliverable, 5131 ATs started the survey (access rate = 10.5%), and 4514 agreed to participate (response rate = 9.3%).
Our study consisted of 6 focus-group sessions, a content-expert review, and a Web-based survey. Themes from the focus groups were used to develop the research priorities and survey instrument. We used the 25-item validated survey to determine whether the research priorities and findings of the focus groups were generalizable. Endorsement of research priorities and recommendations was achieved when respondents indicated they agreed or strongly agreed.
Respondents endorsed 5 research priorities: health care competency (n = 4438/4493, 98.8%), vitality of the profession (n = 4319/4455, 96.9%), health professions education (n = 3966/4419, 89.8%), health care economics (n = 4246/4425, 96.0%), and health information technology (n = 3893/4438, 87.7%). We also made the following recommendations: (1) develop funding initiatives that align with the agenda, (2) develop postdoctoral fellowships focused on clinical research, (3) facilitate collaborative relationships between clinicians and researchers, and (4) make research evidence more readily available and more applicable.
Using a systematic and inclusive process, we developed a prioritized research agenda for the athletic training profession. The agenda was endorsed by the leaders of each Strategic Alliance organization and adopted as the Athletic Training Research Agenda.
Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM ...tasks devoid of interference (Weiss et al., 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proactive interference, such as behavioral inhibition and cognitive flexibility. To distinguish between these possibilities, the same Neo-PRh monkeys and their controls were tested using the Intradimensional/Extradimensional attentional set-shifting task (Roberts et al., 1988; Dias et al., 1997). Neo-PRh monkeys completed the Simple and Compound Discrimination stages, the Intradimensional Shift stage, and all Reversal stages comparably to controls, but made significantly more errors on the Extradimensional Shift stage of the task. These data indicate that impaired cognitive flexibility was the likely source of increased perseverative errors made by Neo-PRh monkeys when performing WM tasks, rather than impaired behavioral inhibition, and imply that the perirhinal cortex and its interactions with the PFC may play a unique and critical role in the development of attentional set shifting abilities.
Studies of the effect of hormone therapy on cognitive function in menopausal women have been equivocal, in part due to differences in the type and timing of hormone treatment. Here we cognitively ...tested aged female rhesus macaques on (1) the delayed response task of spatial working memory, (2) a visuospatial attention task that measured spatially and temporally cued reaction times, and (3) a simple reaction time task as a control for motor speed. After task acquisition, animals were ovariectomized (OVX). Their performance was compared with intact controls for 2 months, at which time no group differences were found. The OVX animals were then assigned to treatment with either a subcutaneous sham implant (OVX), 17-β estradiol (E) implant (OVX+E) or E implant plus cyclic oral progesterone (OVX+EP). All groups were then tested repeatedly over 12 months. The OVX+E animals performed significantly better on the delayed response task than all of the other groups for much of the 12 month testing period. The OVX+EP animals also showed improved performance in the delayed response task, but only at 30 s delays and with performance levels below that of OVX+E animals. The OVX+E animals also performed significantly better in the visuospatial attention task, particularly in the most challenging invalid cue condition; this difference also was maintained across the 12 month testing period. Simple reaction time was not affected by hormonal manipulation. These data demonstrate that chronic, continuous administration of E can exert multiple beneficial cognitive effects in aged, OVX rhesus macaque females.
Hormone therapy after menopause is controversial. We tested the effects of hormone replacement in aged rhesus macaques, soon after surgically-induced menopause ovariectomy (OVX), on tests of memory and attention. Untreated ovarian-intact and OVX animals were compared with OVX animals receiving estradiol (E) alone or E with progesterone (P). E was administered in a continuous fashion via subcutaneous implant, whereas P was administered orally in a cyclic fashion. On both tests, E-treated animals performed better than the other 3 experimental groups across 1 year of treatment. Thus, in this monkey model, chronic E administered soon after the loss of ovarian hormones had long-term benefits for cognitive function.
The perirhinal cortex is known to support high-level perceptual abilities as well as familiarity judgments that may affect recognition memory. We tested whether poor perceptual abilities or a loss of ...familiarity judgment contributed to the recognition memory impairments reported earlier in monkeys with PRh lesions received in infancy (Neo-PRh) (Weiss and Bachevalier, 2016; Zeamer et al., 2015). Perceptual abilities were assessed using a version of the Visual Paired Comparison task with black&white (B&W) stimuli, and familiarity judgments were assessed using the Constant Negative task requiring repeated familiarization exposures. Adult monkeys with Neo-PRh lesions were able to recognize B&W stimuli after short delays, suggesting that their perceptual abilities were within the range of control animals. However, the same Neo-PRh monkeys were slower to acquire the Constant Negative task, requiring more exposures to objects before judging them as familiar compared to control animals. Taken together, the data help to account for the differential patterns of functional compensation on previously reported recognition tasks following neonatal versus adult-onset PRh lesions, and provide further support to the view that the PRh is involved in familiarity processes.
We recently generated a nonhuman primate (NHP) model of the neurodegenerative disorder Huntington's disease (HD) using adeno-associated viral vectors to express a fragment of mutant HTT protein ...(mHTT) throughout the cortico-basal ganglia circuit. Previous work by our group established that mHTT-treated NHPs exhibit progressive motor and cognitive phenotypes which are accompanied by mild volumetric reductions of cortical-basal ganglia structures and reduced fractional anisotropy (FA) in the white matter fiber pathways interconnecting these regions, mirroring findings observed in early-stage HD patients. Given the mild structural atrophy observed in cortical and sub-cortical gray matter regions characterized in this model using tensor-based morphometry, the current study sought to query potential microstructural alterations in the same gray matter regions using diffusion tensor imaging (DTI), to define early biomarkers of neurodegenerative processes in this model. Here, we report that mHTT-treated NHPs exhibit significant microstructural changes in several cortical and subcortical brain regions that comprise the cortico-basal ganglia circuit; with increased FA in the putamen and globus pallidus and decreased FA in the caudate nucleus and several cortical regions. DTI measures also correlated with motor and cognitive deficits such that animals with increased basal ganglia FA, and decreased cortical FA, had more severe motor and cognitive impairment. These data highlight the functional implications of microstructural changes in the cortico-basal ganglia circuit in early-stage HD.
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•We have created a novel AAV-mediated macaque model of Huntington's disease.•High resolution DTI shows significant changes in gray matter of HD macaques.•Diffusion changes in HD macaques correlate with motor and cognitive decline.
•Assessed recognition memory in infant monkeys with neonatal perirhinal lesions using the visual paired comparison task.•Performance was assessed at 4 developmental ages.•Novelty preference ...deteriorated with age after neonatal perirhinal lesions.•Presence of functional sparing.•Memory deficits after perirhinal lesions occurred earlier than after hippocampal lesions.
To investigate the role of the perirhinal cortex on the development of recognition measured by the visual paired-comparison (VPC) task, infant monkeys with neonatal perirhinal lesions and sham-operated controls were tested at 1.5, 6, 18, and 48 months of age on the VPC task with color stimuli and intermixed delays of 10 s, 30 s, 60 s, and 120 s. Monkeys with neonatal perirhinal lesions showed an increase in novelty preference between 1.5 and 6 months of age similar to controls, although at these two ages, performance remained significantly poorer than that of control animals. With age, performance in animals with neonatal perirhinal lesions deteriorated as compared to that of controls. In contrast to the lack of novelty preference in monkeys with perirhinal lesions acquired in adulthood, novelty preference in the neonatally operated animals remained above chance at all delays and all ages. The data suggest that, although incidental recognition memory processes can be supported by the perirhinal cortex in early infancy, other temporal cortical areas may support these processes in the absence of a functional perirhinal cortex early in development. The neural substrates mediating incidental recognition memory processes appear to be more widespread in early infancy than in adulthood.
The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader ...network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but rather impact processes modulating impulse control and/or behavioral flexibility.
The aim of this study was to assess the feasibility of using a commercially available high-resolution adaptive optics (AO) camera to image the cone mosaic in Japanese macaques (Macaca fuscata) with ...dominantly inherited drusen. The macaques examined develop drusen closely resembling those seen in humans with age-related macular degeneration (AMD). For each animal, we acquired and processed images from the AO camera, montaged the results into a composite image, applied custom cone-counting software to detect individual cone photoreceptors, and created a cone density map of the macular region. We conclude that flood-illuminated AO provides a promising method of visualizing the cone mosaic in nonhuman primates. Future studies will quantify the longitudinal change in the cone mosaic and its relationship to the severity of drusen in these animals.
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