A Culture Shift for Excellence in Physical Therapy: Promoting Equity Through the Structural Determinants of Health.

The purpose of this perspective is to discuss the imperative for curricular change that focuses on the utilization of structural competency to promote excellence in physical therapist professional education, transform society, and achieve health equity. Pedagogy centered around biomedical and social determinants of health (SDOH) models are limited in that they lack self-reflexivity, encode social identities like race and gender as risk factors for poor health, fail to examine structural causes of health inequity, conflate SDOH and the structural forces that shape their unequal distribution, and overlook instances of injustice. Promoting health equity will require structural competency, an approach that considers drivers of health beyond the individual and their conditions of daily living (ie, SDOH). Utilizing this approach in physical therapist professional education will help learners understand the evolving needs of society in a deeper, more holistic way: one that considers structural determinants of health as the primary drivers of health equity and inequity. IMPACT: This paper provides a perspective on how physical therapist professional education can promote health equity for all by embracing an equity-focused, structurally competent pedagogy/approach.

Justice, Equity, Diversity, and Inclusion-Related Curricular Elements in Entry-Level Physical Therapist Education: A Delphi Study.

INTRODUCTION: The purpose of this Delphi study was to determine whether experts in justice, equity, diversity, and inclusion (JEDI) in the field of physical therapy could achieve consensus on the key JEDI-related curricular content topics to be included in entry-level physical therapist education. REVIEW OF LITERATURE: Inequities exist at all levels of health care for historically underserved populations, including referrals, access, and quality of physical therapy services. The physical therapy field is facing challenges and opportunities in how to best prepare providers to address individual, community, and population health inequities. There is a lack of consensus in physical therapist education regarding essential curricular content related to justice, equity, diversity, inclusion, and antiracism. SUBJECTS: Eighty-four experts in JEDI in the physical therapy profession were invited through email to participate in the Delphi process. METHODS: A Delphi survey brought together 39 identified experts in justice, equity, diversity, and inclusion within the field of physical therapy to reach consensus on key JEDI-related curricular topics in physical therapist education. In the first-round survey, participants answered an open-ended question: "What JEDI-related curricular content should be included in entry-level physical therapist education?" The work team coded these free-text responses to populate an initial list of curricular elements. Over 2 subsequent rounds of surveys, the experts came to a consensus on which curricular elements should be addressed within physical therapist education. Nineteen experts completed all survey rounds. RESULTS: In round I, coding of the expert group's responses generated 61 initial JEDI-related curricular elements. By round III, the group refined the list to 43 curricular elements; 41 of the 43 (95%) elements garnered 94% or higher consensus. The expert group deemed 30 of the elements "entry-level" content and 13 as more "advanced practice" topics. DISCUSSION AND CONCLUSIONS: Experts had a strong consensus on key JEDI-related curricular elements that physical therapist education programs should include to best prepare providers to improve the health of society. Future scholarship will explore recommendations for how physical therapist education programs might prioritize and implement JEDI-related content.

Acute Responses to High-Intensity Back Squats with Bilateral Blood Flow Restriction.

This study examined the acute effects of high-intensity resistance exercise with blood flow restriction (BFR) on performance and fatigue, metabolic stress, and markers of inflammation (interleukin-6 (IL-6)), muscle damage (myoglobin), angiogenesis (vascular endothelial growth factor (VEGF)). Thirteen resistance-trained participants (four female, 24.8 ± 4.7 years) performed four sets of barbell back-squats (75% 1RM) to failure under two conditions: blood flow restriction (BFR, bilateral 80% occlusion pressure) and control (CTRL). Completed repetitions and pre-post-exercise changes in maximal voluntary isometric contractions, countermovement jump, barbell mean propulsive velocity, and surface electromyography were recorded. Pre-post blood lactate (BLa) and venous blood samples for analysis of IL-6, myoglobin, and VEGF were collected. Ratings of perceived exertion (RPE) and pain were recorded for each set. Fewer repetitions were performed during BFR (25.5 ± 9.6 reps) compared to CTRL (43.4 ± 14.2 reps, p < 0.001), with greater repetitions performed during sets 1, 2, and 4 (p < 0.05) in CTRL. Although RPE between conditions was similar across all sets (p > 0.05), pain was greater in BFR across all sets (p < 0.05). Post-exercise fatigue was comparable between conditions. BLa was significantly greater in CTRL compared to BFR at two minutes (p = 0.001) but not four minutes post-exercise (p = 0.063). IL-6 was significantly elevated following BFR (p = 0.011). Comparable increases in myoglobin (p > 0.05) and no changes in VEGF were observed (p > 0.05). BFR increases the rate of muscular fatigue during high-intensity resistance exercise and acutely enhances IL-6 response, with significantly less total work performed, but increases pain perception, limiting implementation.

Carboxypeptidase E cytoplasmic tail mediates localization of synaptic vesicles to the pre-active zone in hypothalamic pre-synaptic terminals.

How synaptic vesicles (SVs) are localized to the pre-active zone (5-200 nm beneath the active zone) in the nerve terminal, which may represent the slow response SV pool, is not fully understood. Electron microscopy revealed the number of SVs located in the pre-active zone, was significantly decreased in hypothalamic neurons of carboxypeptidase E knockout (CPE-KO) mice compared with wild-type mice. Additionally, we found K(+)-stimulated glutamate secretion from hypothalamic embryonic neurons was impaired in CPE-KO mice. Biochemical studies indicate that SVs from the hypothalamus of wild-type mice and synaptic-like microvesicles from PC12 cells contain a transmembrane form of CPE, with a cytoplasmic tail (CPE(C10)), maybe involved in synaptic function. Yeast two-hybrid and pull-down experiments showed that the CPE cytoplasmic tail interacted with gamma-adducin, which binds actin enriched at the nerve terminal. Total internal reflective fluorescence (TIRF) microscopy using PC12 cells as a model showed that expression of GFP-CPE(C15) reduced the steady-state level of synaptophysin-mRFP containing synaptic-like microvesicles accumulated in the area within 200 nm from the sub-plasma membrane (TIRF zone). Our findings identify the CPE cytoplasmic tail, as a new mediator for the localization of SVs in the actin-rich pre-active zone in hypothalamic neurons and the TIRF zone of PC12 cells.

Role of NMDA, nicotinic, and GABA receptors in the steady-state visual-evoked potential in rats.

Agonists and antagonists at the NMDA, GABA, and nicotinic acetylcholine receptors were administered to adult male rats to evaluate the contribution of these pathways to the visual-evoked potential (VEP). Rats were presented with an onset/offset pattern at a temporal frequency (4.55 Hz) resulting in a steady-state VEP. Averaged VEPs were Fourier transformed and VEP amplitudes were calculated at 1x stimulus frequency (F1) and 2x stimulus frequency (F2). About 30 min after administration, NMDA (10 mg/kg, i.p.; n = 9) increased F1 amplitude by 350% and decreased F2 amplitude by 48%. Memantine (4.5 mg/kg, i.p.; n = 10) increased F1 amplitude by 50%, 10 min post-injection. Similarly, nicotine (0.1 mg/kg, s.c.; n = 9) increased F1 amplitude by 55%, 20 min after drug administration. Muscimol (1 mg/kg, i.p.; n = 10) increased F1 amplitude significantly from 20 to 45 min post-injection. Mecamylamine (6 mg/kg, i.p.; n = 10) decreased F2 amplitude by 70% during the 60-min testing session. Bicuculline (0-0.5 mg/kg, i.p.; n = 8-10 rats/dose) did not significantly alter either F1 or F2 amplitudes. Results indicate important roles for glutamate and nicotinic acetylcholine receptors in both F1 and F2, while GABA receptors contribute to F1.

Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial hyperproinsulinemia.

In familial hyperproinsulinemia, specific mutations in the proinsulin gene are linked with a profound increase in circulating plasma proinsulin levels. However, the molecular and cellular basis for this disease remains uncharacterized. Here we investigated how these mutations may disrupt the sorting signal required to target proinsulin to the secretory granules of the regulated secretory pathway, resulting in the unregulated release of proinsulin. Using a combination of molecular modeling and site-directed mutagenesis, we have identified structural molecular motifs in proinsulin that are necessary for correct sorting into secretory granules of endocrine cells. We show that membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential for proinsulin sorting. This was demonstrated through short interfering RNA-mediated depletion of CPE and transfection with a dominant negative mutant of CPE in a beta-cell line. Mutant proinsulins found in familial hyperproinsulinemia failed to bind to CPE and were not sorted efficiently. These findings provide evidence that the elevation of plasma proinsulin levels found in patients with familial hyperproinsulinemia is caused by the disruption of CPE-mediated sorting of mutant proinsulins to the regulated secretory pathway.

Safety and utilization of blood components as therapeutic delivery systems.

In recent years, natural blood components have been extensively studied as the advanced therapeutic delivery systems. The blood components which can potentially be used as the therapeutic delivery systems include different types of cells, such as erythrocytes and lymphocytes, macromolecular complexes such as lipoproteins and antibody or albumin conjugates and other molecules. This review article covers the progress in this topic, specifically, including the safety issues and the utilization of these component. It can be seen through the literature that the blood components as the therapeutic delivery systems have a number of advantages over traditional pharmaceutical products. The efficacy and practice of the applications, however, require significant amount of development work in the near future.

Change in sexual behavior with provision of no-cost contraception.

OBJECTIVE: To estimate whether providing no-cost contraception is associated with the number of sexual partners and frequency of intercourse over time. METHODS: This was an analysis of the Contraceptive CHOICE Project, a prospective cohort study of 9,256 adolescents and women at risk for unintended pregnancy. Participants were provided reversible contraception of their choice at no cost and were followed-up with telephone interviews at 6 and 12 months. We examined the number of male sexual partners and coital frequency reported during the previous 30 days at baseline compared with 6-month and 12-month time points. RESULTS: From our total cohort, 7,751 (84%) women and adolescents completed both 6-month and 12-month surveys and were included in this analysis. We observed a statistically significant decrease in the fraction of women and adolescents who reported more than one sexual partner during the past 30 days from baseline to 12 months (5.2% to 3.3%; P<.01). Most participants (70-71%) reported no change in their number of sexual partners at 6 and 12 months, whereas 13% reported a decrease and 16% reported an increase (P<.01). More than 80% of participants who reported an increase in the number of partners experienced an increase from zero to one partner. Frequency of intercourse increased during the past 30 days from baseline (median, 4) to 6 and 12 months (median, 6; P<.01). However, greater coital frequency did not result in greater sexually transmitted infection incidence at 12 months. CONCLUSION: We found little evidence to support concerns of increased sexual risk-taking behavior subsequent to greater access to no-cost contraception.

Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina.

Defects in the gene encoding carboxypeptidase E (CPE) in either mouse or human lead to multiple endocrine disorders, including obesity and diabetes. Recent studies on Cpe-/- mice indicated neurological deficits in these animals. As a model system to study the potential role of CPE in neurophysiology, we carried out electroretinography (ERG) and retinal morphological studies on Cpe-/- and Cpe fat/fat mutant mice. Normal retinal morphology was observed by light microscopy in both Cpe-/- and Cpe(fat/fat) mice. However, with increasing age, abnormal retinal function was revealed by ERG. Both Cpe-/- and Cpe fat/fat animals had progressively reduced ERG response sensitivity, decreased b-wave amplitude and delayed implicit time with age, while maintaining a normal a-wave amplitude. Immunohistochemical staining showed specific localization of CPE in photoreceptor synaptic terminals in wild-type (WT) mice, but in both Cpe-/- and Cpe fat/fat mice, CPE was absent in this layer. Bipolar cell morphology and distribution were normal in these mutant mice. Electron microscopy of retinas from Cpe fat/fat mice revealed significantly reduced spherule size, but normal synaptic ribbons and synaptic vesicle density, implicating a reduction in total number of vesicles per synapse in the photoreceptors of these animals. These results suggest that CPE is required for normal-sized photoreceptor synaptic terminal and normal signal transmission to the inner retina.