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The objective of this study was to evaluate the pathology time course of the LRRK2 knockout rat model of Parkinson's disease at 1-, 2-, 4-, 8-, 12-, and 16-months of age. The evaluation consisted of histopathology and ultrastructure examination of selected organs, including the kidneys, lungs, spleen, heart, and liver, as well as hematology, serum, and urine analysis. The LRRK2 knockout rat, starting at 2-months of age, displayed abnormal kidney staining patterns and/or morphologic changes that were associated with higher serum phosphorous, creatinine, cholesterol, and sorbitol dehydrogenase, and lower serum sodium and chloride compared to the LRRK2 wild-type rat. Urinalysis indicated pronounced changes in LRRK2 knockout rats in urine specific gravity, total volume, urine potassium, creatinine, sodium, and chloride that started as early as 1- to 2-months of age. Electron microscopy of 16-month old LRRK2 knockout rats displayed an abnormal kidney, lung, and liver phenotype. In contrast, there were equivocal or no differences in the heart and spleen of LRRK2 wild-type and knockout rats. These findings partially replicate data from a recent study in 4-month old LRRK2 knockout rats and expand the analysis to demonstrate that the renal and possibly lung and liver abnormalities progress with age. The characterization of LRRK2 knockout rats may prove to be extremely valuable in understanding potential safety liabilities of LRRK2 kinase inhibitor therapeutics for treating Parkinson's disease.

System x c - (with xCT as specific subunit) is an astrocytic cystine/glutamate antiporter that constitutes the major source of extracellular glutamate in the mouse striatum. We previously reported that young-adult mice lacking xCT (xCT -/- mice) display decreased intracellular glutamate levels in pre- and post-synaptic compartments at corticostriatal synapses as well as impaired corticostriatal neurotransmission, compared to wildtype (xCT +/+ ) littermates. These changes were accompanied by increased repetitive behavior and reduced social interaction, typical behaviors related to autism spectrum disorder (ASD). Although ASD is reported to be associated with atypical brain aging, we recently showed that xCT -/- mice are protected against age-related hippocampal decline. Therefore, we here investigated whether the corticostriatal impairments and associated ASD-like behavior would be maintained in aged (16-months-old) mice. Genetic deletion of xCT does not affect corticostriatal neurotransmission in aged mice or the morphology of medium-spiny neurons. Except for a slight decrease in synaptic cleft width, the ultrastructure of corticostriatal synapses and intracellular glutamate levels are unaltered in the absence of xCT in aged mice. Accordingly, repetitive and social explorative behavior were comparable between aged xCT +/+ and xCT -/- mice, while the latter showed a reduction in interactions that could be classified as being aggressive or dominant. To conclude, contrary to our previous observations in young-adult mice, corticostriatal neurotransmission and social behavior are no longer impaired in aged xCT -/- mice, most likely because intracellular glutamate levels are no longer different. Moreover, the reduced levels of advanced glycation end-products that we observed in striatal tissue of xCT -/- mice, can protect the xCT -/- brain from age-related pathogenic alterations.

Objective To determine whether an enhanced recovery after surgery (ERAS) nutrition protocol is reasonably possible among our head and neck cancer (HNC) population with respect to system feasibility and patient compliance. Second, we aim to identify improvements in patient outcomes as a result. Methods Preexperimental research design among patients undergoing major HNC surgery after implementation of the ERAS nutrition protocol from July 2018 to July 2019 as quality improvement (QI). Preoperative clinical nutritional assessment and laboratory values were completed the same day as informed surgical consent in the clinic. Protocol focus was patient consumption of nutritional supplements perioperatively, monitored by our outpatient dietitian. Early postoperative enteral nutrition was initiated with monitoring of nutritional laboratory values. To support our model, we provide preliminary analysis of HNC patient outcomes after implementation of the ERAS nutritional protocol. Results Twenty-five patients were enrolled. Preoperatively, 40% of patients were malnourished, and 100% complied with perioperative nutrition supplementation. Health care provider compliance obtaining preoperative laboratory values was 56%. There was a strong negative correlation between modified Nutrition-Related Index (mNRI) and number of complications (P = .01), specifically, fistula rate (P = .04) and unplanned reoperation (P = .04). Enrolled patient average length of stay was 7 ± 4.4 days. Discussion Our patients demonstrated compliance with implementation of an ERAS nutrition protocol likely facilitated by dietitian engagement. mNRI potentially reflects risk for head and neck surgery complications. Implications for Practice QI processes demand reassessment and modification to ensure efficient and targeted approaches to improving patient care.

Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission.

Abstract Shared decision making (SDM) has been associated with increased patient satisfaction and engagement and improved process and care outcomes. However, SDM use by physical therapists (PTs) working with older adults in the home care setting is not known. Understanding home care PTs' views about and experiences with SDM, including inter-professional SDM, can inform SDM research and strategies for increasing its use. This presentation highlights inter-professional aspects of SDM described by home care PTs in the qualitative arm of a mixed methods, implementation science frameworks-informed study exploring PTs' perspectives on SDM in home care. Semi-structured interview data from twenty PTs (80% female; mean age = 50.6, SD=12.7, range 28-73) representing all geographic regions of the continental United States and having varied levels of geriatric (mean 24.2 years, SD=11.6, range 3-40) and home care (mean 15.7, SD=11.5, range 2-40) experience were analyzed using thematic content analysis. A trustworthiness plan guided data collection and analysis, and reflexive journaling, memo, audit trail, peer debriefing, data triangulation, and member checking were used to support study rigor. Three inter-professional SDM-related themes were identified: team members facilitating SDM for all disciplines; within-team sharing of and competition for patient care resources; and limited patient/caregiver participation in team treatment planning decisions. Findings support the need for including inter-professional issues in home care SDM implementation and measurement research and suggest topics to include in future studies.

Moore discusses the case study of an 84-year-old man who was referred by his primary care physician to home care physical and occupational therapy to address limited ambulation, transfers, and ADLs. He meets the eligibility requirements for Medicare Part A services. His stated goal is to improve his walking distance, steadiness, and engage in more active play with his adolescent-aged grandchildren. The man lives in a one-story home with his wife who performs all the household IADLs and assists him with ADLs as needed. His wife reports that her husband fell 5 days ago in the living room while she was in the kitchen preparing dinner. She states that even though he had no pain and did not appear injured, she was \"not able to pick him up\" and so she called 911.

Abstract Study Objectives In previous work, dietary branched-chain amino acid (BCAA) supplementation, precursors to de novo glutamate and γ-aminobutyric acid (GABA) synthesis, restored impaired sleep–wake regulation and orexin neuronal activity following traumatic brain injury (TBI) in mice. TBI was speculated to reduce orexin neuronal activity through decreased regional excitatory (glutamate) and/or increased inhibitory (GABA) input. Therefore, we hypothesized that TBI would decrease synaptic glutamate and/or increase synaptic GABA in nerve terminals contacting orexin neurons, and BCAA supplementation would restore TBI-induced changes in synaptic glutamate and/or GABA. Methods Brain tissue was processed for orexin pre-embed diaminobenzidine labeling and glutamate or GABA postembed immunogold labeling. The density of glutamate and GABA immunogold within presynaptic nerve terminals contacting orexin-positive lateral hypothalamic neurons was quantified using electron microscopy in three groups of mice (n = 8 per group): Sham/noninjured controls, TBI without BCAA supplementation, and TBI with BCAA supplementation (given for 5 days, 48 hr post-TBI). Glutamate and GABA were also quantified within the cortical penumbral region (layer VIb) adjacent to the TBI lesion. Results In the hypothalamus and cortex, TBI decreased relative glutamate density in presynaptic terminals making axodendritic contacts. However, BCAA supplementation only restored relative glutamate density within presynaptic terminals contacting orexin-positive hypothalamic neurons. BCAA supplementation did not change relative glutamate density in presynaptic terminals making axosomatic contacts, or relative GABA density in presynaptic terminals making axosomatic or axodendritic contacts, within either the hypothalamus or cortex. Conclusions These results suggest TBI compromises orexin neuron function via decreased glutamate density and highlight BCAA supplementation as a potential therapy to restore glutamate density to orexin neurons.

System x (with xCT as specific subunit) is an astrocytic cystine/glutamate antiporter that constitutes the major source of extracellular glutamate in the mouse striatum. We previously reported that young-adult mice lacking xCT (xCT mice) display decreased intracellular glutamate levels in pre- and post-synaptic compartments at corticostriatal synapses as well as impaired corticostriatal neurotransmission, compared to wildtype (xCT ) littermates. These changes were accompanied by increased repetitive behavior and reduced social interaction, typical behaviors related to autism spectrum disorder (ASD). Although ASD is reported to be associated with atypical brain aging, we recently showed that xCT mice are protected against age-related hippocampal decline. Therefore, we here investigated whether the corticostriatal impairments and associated ASD-like behavior would be maintained in aged (16-months-old) mice. Genetic deletion of xCT does not affect corticostriatal neurotransmission in aged mice or the morphology of medium-spiny neurons. Except for a slight decrease in synaptic cleft width, the ultrastructure of corticostriatal synapses and intracellular glutamate levels are unaltered in the absence of xCT in aged mice. Accordingly, repetitive and social explorative behavior were comparable between aged xCT and xCT mice, while the latter showed a reduction in interactions that could be classified as being aggressive or dominant. To conclude, contrary to our previous observations in young-adult mice, corticostriatal neurotransmission and social behavior are no longer impaired in aged xCT mice, most likely because intracellular glutamate levels are no longer different. Moreover, the reduced levels of advanced glycation end-products that we observed in striatal tissue of xCT mice, can protect the xCT brain from age-related pathogenic alterations.

Objective: Shared decision making (SDM) in physical therapy can improve patient outcomes and satisfaction but is underutilized. This study describes the views of home care physical therapists (PTs) regarding older adult patients’ participation in therapy goal setting and treatment planning. Methods: A convergent mixed methods approach was used. Physical therapists’ SDM knowledge, skills, attitudes, use, and barriers were surveyed in an online questionnaire informed by an SDM in physical therapy framework and two implementation science frameworks. Semi-structured interviews were analyzed using conventional content analysis, and a trustworthiness plan supported study rigor. Results: Surveys were completed by 220 PTs of varied age (range 27-76 years, mean 49.1 ± 11.58) and experience (range 1-49 years, mean 23.6 ± 12.32) who provided home care services to older adults in 44 states. Twenty PTs (80% female; mean age = 50.6, SD=12.7, range 28-73) representing all continental United States geographic regions with varied levels of geriatric (mean 24.2 years, SD=11.6, range 3-40) and home care (mean 15.7, SD=11.5, range 2-40) experience were interviewed. As measured by SDM-Q-Doc, SDM was present (adjusted score 70.0% ± 17.25) and correlated with 12 factors including respondents’ rating of their patients’ overall desired (r=.418, p<.001) and actual (r=.409, p<.001) levels of participation in goal setting. Therapists viewed SDM as beneficial and part of their professional role, but encountered patient, clinician, and organizational barriers to increasing its use. Missed opportunities for understanding and meeting patients’ needs and tensions between clinical judgments and organizational requirements were identified. A table of SDM barriers and strategies was constructed from the data and a conceptual model was developed to illustrate types and flow of goal and treatment decisions. Conclusions: Findings show room for increased SDM and suggest interventions addressing PTs’ professional role, their ability to collaboratively weigh treatment options, affirm shared decisions, and translate patients’ aspirational goals to goals into ones acceptable to regulators and payers. Home care physical therapy SDM frameworks, measurement tools, and interventions need to address goal setting as well as treatment planning, accommodate differences between setting patient and therapeutic goals, and acknowledge the role of actors beyond therapist-patient dyads.

By now, the idea that teaching, like learning, is a complex activity—and should be evaluated as such—is common knowledge among educators. We’ve known for decades that, in order to draw accurate, fair conclusions about a teacher’s effectiveness, we need to both “consult” a variety of information “sources” (e.g., students, colleagues, administrators, the teacher herself) and use “ multiple measures” of teaching effectiveness, including teaching materials, class observation reports, and actual student work (Seldin 1984, 132; see also Seldin et al. 1990). With respect to rhetoric and composition, these principles informed early assertions that “ teachers should never be