Assessing the benefits of an online prematriculation anatomy workshop on knowledge acquisition and anatomy competency in a Doctor of Physical Therapy program.

Preparing students for the transition to graduate-level education with greater learning demands in a condensed time frame is a challenging process for health professions educators and incoming students. Prematriculation programs offer a solution for exposing students to the foundational sciences in preparation for the academic rigor of a doctoral program. This retrospective study assessed whether incoming students enrolled across 3 yr of a 2-day online anatomy workshop, offered in July and August before the start of their first semester resulted in improved anatomy knowledge. Whether this acquired knowledge translated to improved anatomy outcomes in the first semester of a Doctor of Physical Therapy program was also assessed, while also accounting for variables of gender, ethnicity, and grade-point average. Knowledge acquired during both days of the workshop resulted in statistically significant improvements in anatomy postquiz scores compared to the baseline prequiz (P < 0.001). Multivariate regression analyses demonstrated statistically significant relationships between the first-semester anatomy practical score and workshop participation (P = 0.04) as well as a predictive value of gender (P = 0.01). Evaluating a timing effect on the predictive value of the online anatomy workshop demonstrated statistically significant effects of the prematriculation workshop on both first-semester anatomy practicals for August (P = 0.03 for practical 1; P = 0.04 for practical 2) but not July workshop participants. Findings from this study support the utility of an online prematriculation anatomy workshop to prepare students for graduate-level anatomy learning expectations in a doctoral allied health program.NEW & NOTEWORTHY This paper presents the findings of a retrospective study examining the effectiveness of an online prematriculation anatomy workshop on knowledge acquisition and first-semester anatomy competency following the success of a previously offered peer-led onsite workshop. To our knowledge, this is the first report of an online prematriculation program that successfully introduces graduate-level learning expectations and access to anatomical resources leading to improved anatomy competency in an allied health professional program.

Association Between Ethnic-Racial Minority Status, Admissions Data, and Academic Performance in Student Retention from a Physical Therapy Program in a Minority-Serving Institution.

Ethnic-racial under-represented students (URM) exhibit greater attrition rates from physical therapy (PT) doctoral programs. Most predictive analytics in PT education are based on predictors of success in passing the licensure examination. However, data predicting the reasons why these groups of URM students withdraw from PT school are scarce. Admissions variables and academic perform¬ance of seven entry-level Doctor of Physical Therapy (DPT) cohorts (n = 191) from a US university were analyzed from their application and admission through graduation or withdrawal from the program. Through a binary logistic regression, it was found that the main predictors of with¬drawal from the DPT program were URM status (X2 = 8.77; p = 0.004; OR = 21.4) and failing the first practical exam (X2 = 12.30; p < 0.001; OR = 14.2). Those from URM back¬grounds were more than 20 times more likely to withdraw from PT school, while failing the first clinical practical exam increased 14 times the odds of withdrawing from PT school. Admission criteria and targeted retention strategies need to be addressed to ensure the success of URM students to ensure a more diverse PT workforce.

Effect of self-regulated learning and technology-enhanced activities on anatomy learning, engagement, and course outcomes in a problem-based learning program.

Problem-based learning (PBL) offers advantages for teaching anatomy and physiology for physical therapy students as clinical cases provide a scaffold for a comprehensive review of body systems. Although the utilization of interactive anatomy software greatly contributes to an active learning environment and efficient use of time, simply providing textbook readings, access to anatomy software, and models is not enough to engage students to become active in reaching their learning goals. Time constraints, meaningful technology implementation, resource abundance, and unfamiliarity are challenges that decrease the effectiveness of both facilitating and learning anatomy. The present study investigated the use of three supplemental learning tools to support anatomy instruction in a self-regulated manner. Friedman test results demonstrated significant differences for perceived engagement [χ2(2) = 15.74, P < 0.001, W = 0.23] but not for perceived learning. Survey responses demonstrated that perceived engagement was greatest with the nondigital supplemental learning tool compared with the two technology-enhanced learning tools (iBooks Author + SoftChalk and SoftChalk alone). Multivariate regression analyses demonstrated statistically significant relationships between the nondigital supplemental learning tool and anatomy practical scores (P < 0.001). The technology-enhanced supplemental learning tools did not further increase learning outcomes as measured by practical scores compared with nondigital learning tools. Incorporation of instructor-created instructional materials independent of technology is an efficient method to drive self-regulated learning, enhance engagement, and improve anatomy course outcomes and may overcome barriers associated with a purely self-directed PBL model.

The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials.

BACKGROUND AND PURPOSE: The role of creatine supplementation in young athletes and bodybuilders is well established including ergogenic properties of muscular hypertrophy, strength, power, and endurance. Whether the benefits of creatine supplementation translate to an aging population with moderate training stimulus remains unclear especially in regard to gender, creatine dose, and duration. This systematic review assessed whether creatine supplementation combined with exercise results in additive improvements in indices of skeletal muscle, bone, and mental health over exercise alone in healthy older adults. METHODS: PubMed, CINAHL, and Web of Science databases were utilized to identify randomized controlled trials of creatine supplementation combined with exercise in an aging population with additional predetermined inclusion and exclusion criteria. Two reviewers independently screened the titles and abstracts, reviewed full-text articles, and performed quality assessments using the Physiotherapy Evidence Database scale. RESULTS AND DISCUSSION: Seventeen studies were comprehensively reviewed according to categories of strength, endurance, functional capacity, body composition, cognition, and safety. These studies suggest that any additive ergogenic creatine effects on upper and/or lower body strength, functional capacity, and lean mass in an older population would require a continuous and daily low-dose creatine supplementation combined with at least 12 weeks of resistance training. Potential creatine specific increases in regional bone mineral density of the femur are possible but may require at least 1 year of creatine supplementation combined with moderate resistance training, and additional long-term clinical trials are warranted. The limited data suggested no additive effects of creatine over exercise alone on indices of mental health. The beneficial effects of creatine supplementation are more consistent in older women than in men. CONCLUSIONS: Creatine monohydrate is safe to use in older adults. While creatine in conjunction with moderate- to high-intensity exercise in an aging population may improve skeletal muscle health, additional studies are needed to determine the effective dosing and duration paradigm for potential combined creatine and exercise effects on bone and cognition in older adults.

An anatomy workshop for improving anatomy self-efficacy and competency when transitioning into a problem-based learning, Doctor of Physical Therapy program.

First-year Doctor of Physical Therapy (DPT) students entering a problem-based learning (PBL) program are faced with a number of pedagogical challenges, including the development of self-directed learning skills, resource unfamiliarity, and group dynamics. These challenges can make learning anatomy in a self-directed manner less efficient. Prematriculation introduction of strategies to improve anatomy learning may help prepare students for a rigorous DPT program and improve anatomy learning efficiency. The present study describes a 2-day anatomy workshop offered to incoming students before a DPT program was initiated. Knowledge acquired during both days of the workshop resulted in statistically significant improvements in anatomy postquiz scores for each corresponding prequiz (P < 0.001 for lower and upper limb quizzes). Workshop participants survey responses demonstrated that anatomy confidence and PBL preparedness increased at distinct intervals following the workshop and was significantly higher than controls after the first semester (P < 0.01 for anatomy confidence and PBL preparedness). Multivariate regression analyses demonstrated statistically significant relationships between semester anatomy practical scores and workshop participation (P = 0.03 for practical 1 and P = 0.049 for practical 2) and undergraduate grade point average (P < 0.001 for practical 1 and P = 0.03 for practical 2). First-year DPT students reported the anatomy workshop to be a valuable experience for learning strategies to improve anatomy self-efficacy. An introductory anatomy workshop is an effective strategy to improve self-directed anatomy learning efficiency before the start of a rigorous DPT program.

Estrogen protects against dopamine neuron toxicity in primary mesencephalic cultures through an indirect P13K/Akt mediated astrocyte pathway.

Astrocytes regulate neuronal homeostasis and have been implicated in affecting the viability and functioning of surrounding neurons under stressed and injured conditions. Previous data from our lab suggests indirect actions of estrogen through ERα in neighboring astroglia to protect dopamine neurons against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity in mouse mesencephalic cultures. We further evaluate estrogen signaling in astrocytes and the mechanism of estrogen's indirect neuroprotective effects on dopamine neurons. Primary mesencephalic cultures pre-treated with 17ß-estradiol and the membrane impermeable estrogen, E2-BSA, were both neuroprotective against MPP(+) -induced dopamine neuron toxicity, suggesting membrane-initiated neuroprotection. ERα was found in the plasma membrane of astrocyte cultures and colocalized with the lipid raft marker, flotillin-1. A 17ß-estradiol time course revealed a significant increase in Akt, which was inhibited by the PI3 kinase inhibitor, LY294004. Estrogen conditioned media collected from pure astrocyte cultures rescued glial deficient mesencephalic cultures from MPP(+). This indirect estrogen-mediated neuroprotective effect in mesencephalic cultures was significantly reduced when PI3 kinase signaling in astrocytes was blocked prior to collecting estrogen-conditioned media using the irreversible PI3 kinase inhibitor, Wortmannin. Estrogen signaling via astrocytes is rapidly initiated at the membrane level and requires PI3 kinase signaling in order to protect primary mesencephalic dopamine neurons from MPP(+) neurotoxicity.

Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model.

The efficacy of the amphipathic ketoamide calpain inhibitor SNJ-1945 in attenuating calpain-mediated degradation of the neuronal cytoskeletal protein α-spectrin was examined in the controlled cortical impact (CCI) traumatic brain injury (TBI) model in male CF-1 mice. Using a single early (15 min after CCI-TBI) i.p. bolus administration of SNJ-1945 (6.25, 12.5, 25, or 50-mg/kg), we identified the most effective dose on α-spectrin degradation in the cortical tissue of mice at its 24 h peak after severe CCI-TBI. We then investigated the effects of a pharmacokinetically optimized regimen by examining multiple treatment paradigms that varied in dose and duration of treatment. Finally, using the most effective treatment regimen, the therapeutic window of α-spectrin degradation attenuation was assessed by delaying treatment from 15 min to 1 or 3 h post-injury. The effect of SNJ-1945 on α-spectrin degradation exhibited a U-shaped dose-response curve when treatment was initiated 15 min post-TBI. The most effective 12.5 mg/kg dose of SNJ-1945 significantly reduced α-spectrin degradation by ~60% in cortical tissue. Repeated dosing of SNJ-1945 beginning with a 12.5 mg/kg dose did not achieve a more robust effect compared with a single bolus treatment, and the required treatment initiation was less than 1 h. Although calpain has been firmly established to play a major role in post-traumatic secondary neurodegeneration, these data suggest that even brain and cell-permeable calpain inhibitors, when administered alone, do not show sufficient cytoskeletal protective efficacy or a practical therapeutic window in a mouse model of severe TBI. Such conclusions need to be verified in the human clinical situation.

Antioxidant therapies in traumatic brain and spinal cord injury.

Free radical formation and oxidative damage have been extensively investigated and validated as important contributors to the pathophysiology of acute central nervous system injury. The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following injury occurring within minutes of mechanical impact. A key component in this event is peroxynitrite-induced lipid peroxidation. As discussed in this review, peroxynitrite formation and lipid peroxidation irreversibly damages neuronal membrane lipids and protein function, which results in subsequent disruptions in ion homeostasis, glutamate-mediated excitotoxicity, mitochondrial respiratory failure and microvascular damage. Antioxidant approaches include the inhibition and/or scavenging of superoxide, peroxynitrite, or carbonyl compounds, the inhibition of lipid peroxidation and the targeting of the endogenous antioxidant defense system. This review covers the preclinical and clinical literature supporting the role of ROS and RNS and their derived oxygen free radicals in the secondary injury response following acute traumatic brain injury (TBI) and spinal cord injury (SCI) and reviews the past and current trends in the development of antioxidant therapeutic strategies. Combinatorial treatment with the suggested mechanistically complementary antioxidants will also be discussed as a promising neuroprotective approach in TBI and SCI therapeutic research. This article is part of a Special Issue entitled: Antioxidants and antioxidant treatment in disease.

Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson's disease.

Mutations in parkin, an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. Activated c-Abl was found in the striatum of PD patients. Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2 (aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo. Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression.

IGF-I stimulates Rab7-RILP interaction during neuronal autophagy.

Restoration of autophagy represents a potential therapeutic target for neurodegenerative disorders, but factors that regulate autophagic flux are largely unknown. When deprived of trophic factors, cultured Purkinje neurons die by an autophagy associated cell death mechanism. The accumulation of autophagic vesicles and cell death of Purkinje neurons is inhibited by insulin-like growth factor, by a mechanism that enhances autophagic vesicle turnover. In this report, we identify Rab7 as an IGF-I regulated target during neuronal autophagy. Purkinje neurons transfected with EGFP-Rab7-WT and constitutively active EGFP-Rab7-Q67L contained few RFP-LC3 positive autophagosomes and little co-localization with GFP-Rab7 under control conditions. Upon induction of autophagy, RFP-LC3 positive autophagosomes increased and co-localized with GFP-Rab7. Conversely, expression of the dominant negative mutant EGFP-Rab7-T22N increased the accumulation of autophagosomes under control conditions, which accumulated even further during trophic factor withdrawal. There was no vesicular co-localization between Rab7-T22N and RFP-LC3 under control or trophic factor withdrawal conditions. During prolonged trophic factor withdrawal, a condition that leads to the accumulation of autophagic vesicles and cell death, Rab7 activity decreased significantly. IGF-I, added at the time of trophic factor withdrawal, prevented the deactivation of Rab7 and increased the interaction of Rab7 with its interacting protein (RILP), restoring autophagic flux. These results provide a novel mechanism by which IGF-I regulates autophagic flux during neuronal stress.

A pharmacological analysis of the neuroprotective efficacy of the brain- and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model.

The cytoskeletal and neuronal protective effects of early treatment with the blood-brain barrier- and cell-permeable calpain inhibitor MDL-28170 was examined in the controlled cortical impact (CCI) traumatic brain injury (TBI) model in male CF-1 mice. This was preceded by a dose-response and pharmacodynamic evaluation of IV or IP doses of MDL-28170 with regard to ex vivo inhibition of calpain 2 activity in harvested brain homogenates. From these data, we tested the effects of an optimized MDL-28170 dosing regimen on calpain-mediated degradation of the neuronal cytoskeletal protein α-spectrin in cortical or hippocampal tissue of mice 24 h after CCI-TBI (1.0 mm depth, 3.5 m/sec velocity). With treatment initiated at 15 min post-TBI, α-spectrin degradation was significantly reduced by 40% in hippocampus and 44% in cortex. This effect was still observed with a 1-h but not a 3-h post-TBI delay. The cytoskeletal protection is most likely taking place in neurons surrounding the area of mainly necrotic degeneration, since MDL-28170 did not reduce hemispheric lesion volume as measured by the aminocupric silver staining method. This lack of effect on lesion volume has been seen with other calpain inhibitors, which suggests that pharmacological calpain inhibition by itself, while able to reduce axonal injury, may not be able to produce a measurable reduction in lesion volume. This is in contrast to certain other neuroprotective mechanistic approaches such as the mitochondrial protectant cyclosporine A, which produces at least a partial decrease in lesion volume in the same model. Accordingly, the combination of a calpain inhibitor with a compound such as cyclosporine A may be needed to achieve the optimal degree of post-TBI neuroprotection.

Insulin-like growth factor-I prevents the accumulation of autophagic vesicles and cell death in Purkinje neurons by increasing the rate of autophagosome-to-lysosome fusion and degradation.

Continuous macroautophagic activity is critical for the maintenance of neuronal homeostasis; however, unchecked or dysregulated autophagy can lead to cell death. Cultured Purkinje neurons die by an autophagy-associated cell death mechanism when deprived of trophic support. Here, we report that insulin-like growth factor-I (IGF-I) completely blocked the autophagy-associated cell death of Purkinje neurons. To examine the mechanism by which IGF-I influences autophagy, neurons were infected with adeno-RFP-LC3 and subjected to trophic factor withdrawal, and the size and number of autophagosomes were analyzed by live-cell fluorescence imaging. In control neurons, autophagy occurred at a constitutive low level with most autophagosomes measuring less than 0.75 microm. Trophic factor withdrawal increased the number and size of autophagosomes with most autophagosomes ranging between 0.75 and 1.5 microm and some reaching 1.5-2.25 microm. IGF-I added at the time of trophic factor withdrawal prevented the accumulation of the larger autophagosomes; however, it had no effect on the conversion of LC3, an indicator of autophagy induction. Instead, the rate of autophagosome-to-lysosome fusion measured by colocalization of RFP-LC3 and LysoSensor Green was accelerated by IGF-I. Treating the neurons with bafilomycin A(1) in the presence of IGF-I led to the accumulation of autophagosomes even larger than those induced by trophic factor withdrawal alone, indicating that IGF-I regulates autophagic vesicle turnover. Finally, the effect of IGF-I on autophagy was mediated by an Akt/mTOR-de pend ent and an ERK-independent pathway. These data suggest a novel role for IGF-I in protecting Purkinje neurons from autophagy-associated cell death by increasing autophagy efficiency downstream of autophagy induction.

Live-cell imaging of autophagy induction and autophagosome-lysosome fusion in primary cultured neurons.

The discovery that impaired autophagy is linked to a wide variety of prominent diseases including cancer and neurodegeneration has led to an explosion of research in this area. Methodologies that allow investigators to observe and quantify the autophagic process will clearly advance knowledge of how this process contributes to the pathophysiology of many clinical disorders. The recent identification of essential autophagy genes in higher eukaryotes has made it possible to analyze autophagy in mammalian cells that express autophagy proteins tagged with fluorescent markers. This chapter describes such methods using primary cultured neurons that undergo up-regulation of autophagy when trophic factors are removed from their medium. The prolonged up-regulated autophagy, in turn, contributes to the death of these neurons, thus providing a model to examine the relationship between enhanced autophagy and cell death. Neurons are isolated from the cerebellum of postnatal day 7 rat pups and cultured in the presence of trophic factors and depolarizing concentrations of potassium. Once established, the neurons are transfected with an adeno-viral vector expressing MAP1-LC3 with red fluorescent protein (RFP). MAP1-LC3 is the mammalian homolog of the yeast autophagosomal marker Atg8 and when tagged to GFP or RFP, it is the most widely used marker for autophagosomes. Once expression is stable, autophagy is induced by removing trophic factors. At various time points after inducing autophagy, the neurons are stained with LysoSensor Green (a pH-dependent lysosome marker) and Hoechst (a DNA marker) and subjected to live-cell imaging. In some cases, time-lapse imaging is used to examine the stepwise process of autophagy in live neurons.

Neuroprotection by estrogen against MPP+-induced dopamine neuron death is mediated by ERalpha in primary cultures of mouse mesencephalon.

Estrogen involvement in neuroprotection is now widely accepted, although the specific molecular and cellular mechanisms of estrogen action in neuroprotection remain unclear. This study examines estrogenic effects in a mixed population of cells in attempts to identify the contributing cells that result in estrogen-mediated neuroprotection. Utilizing primary mesencephalic neurons, we found expression of both estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) with a predominance of ERalpha on both dopamine neurons and astrocytes. We also found that 17beta-estradiol protects dopamine neurons from injury induced by the complex I inhibitor, 1-methyl-4-phenyl pyridinium (MPP(+)) in a time- and ER-dependent manner. At least 4 h of estrogen pre-treatment was required to elicit protection, an effect that was blocked by the ER antagonist, ICI 182,780. Moreover, ERalpha mediated the protection afforded by estrogen since only the ERalpha agonist, HPTE, but not the ERbeta agonist, DPN, protected against dopamine cell loss. Since glial cells were shown to express significant levels of ERalpha, we investigated a possible indirect mechanism of estrogen-mediated neuroprotection through glial cell interaction. Removal of glial cells from the cultures by application of the mitotic inhibitor, 5-fluoro-2'-deoxyuridine, significantly reduced the neuroprotective effects of estrogen. These data indicate that neuroprotection provided by estrogen against MPP(+) toxicity is mediated by ERalpha and involves an interplay among at least two cell types.