Creating the HAPS Physiology Learning Outcomes: terminology, eponyms, inclusive language, core concepts, and skills.

Learning outcomes are an essential element in curriculum development because they describe what students should be able to do by the end of a course or program and they provide a roadmap for designing assessments. This article describes the development of competency-based learning outcomes for a one-semester undergraduate introductory human physiology course. Key elements in the development process included decisions about terminology, eponyms, use of the word "normal," and similar considerations for inclusivity. The outcomes are keyed to related physiology core concepts and to process skills that can be taught along with the content. The learning outcomes have been published under a Creative Commons license by the Human Anatomy and Physiology Society (HAPS) and are available free of charge on the HAPS website.NEW & NOTEWORTHY This article describes the development of competency-based learning outcomes for introductory undergraduate human physiology courses that were published and made available free of charge by the Human Anatomy and Physiology Society (HAPS). These learning outcomes can be edited and are keyed to physiology core concepts and to process skills that can be taught along with the content.

Understanding carpal tunnel syndrome.

ABSTRACT: Carpal tunnel syndrome (CTS) is an entrapment neuropathy affecting the median nerve. Prevalence is estimated at 4% to 5% of the population. A solid understanding of the anatomy, presentation, and diagnostics is key to efficient diagnosis and appropriate referral. Both surgical and nonsurgical interventions have led to improved clinical outcomes. Clinicians who have an in-depth knowledge of CTS symptoms and treatment options can prepare patients and streamline referrals for improved patient outcomes.

Direct care TeleDiabetes practice in the Phoenix VA healthcare system: Innovation report.

The Phoenix Veterans Affairs Healthcare System implemented a TeleDiabetes program in 2018 to provide multidisciplinary care to rural Veterans with type 2 diabetes. Here, we introduce the TeleDiabetes program as a novel telemedicine model with integrated remote physical exam, and we share results demonstrating Veteran satisfaction with the program.

Characterizing Occult Nodal Disease Within a Clinically Node-Negative, Neoadjuvant Breast Cancer Population.

BACKGROUND: Neoadjuvant therapy aims to preoperatively downstage breast cancer patients. We evaluated nodal upstaging in clinically node-negative (cN0) patients receiving neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy (NET). METHODS: cN0 patients undergoing neoadjuvant therapy from 2009 to 2018 were reviewed. Univariate and multivariate analyses evaluated rates of nodal upstaging. RESULTS: A total of 228 cN0 patients with a mean age of 55 years underwent neoadjuvant therapy for Stage I-III invasive carcinoma. Subtypes included ER+/HER2- = 93 (40%), HER2+ = 61 (27%), and triple negative (TNBC) = 74 (33%). Among ER+/HER2- patients, 65 (70%) underwent NET. Overall, 49 patients (21%) were upstaged due to occult nodal disease. Factors associated with higher rates of occult nodal disease included advanced stage on initial presentation (P = .008), larger presenting tumor size (P = .009), low/intermediate tumor grade (P = .025), and ER+/HER2- subtype (P < .001); incidence of occult nodal disease by subtype included: ER+/HER2- = 37%, HER2+ = 15%, TNBC = 8%. Patients experiencing a breast pCR had a significantly lower rate of nodal upstaging compared to those with residual tumor (4% vs. 96%, P < .001). On multivariate analysis, ER+/HER- patients exhibited higher risk of occult nodal disease when compared to patients with HER2+ (odds ratio [OR] = 3.4, 95% CI, 1.2-9.8, P = .003) and TNBC (OR = 5.7, 95% CI, 1.7-19.6, P = .003). Comparing NAC vs. NET in ER+/HER2- patients showed no difference in rates of occult nodal disease (39% vs. 35%, P = .13). CONCLUSIONS: ER+/HER2- subtype carries higher risk for occult nodal disease after neoadjuvant therapy; NAC versus NET in these patients does not affect nodal upstaging.

Air Quality Is Predictive of Mistakes in Professional Baseball and American Football.

Air quality is a growing environmental concern that has implications for human physical and mental health. While air pollution has been linked to cognitive disease progression and declines in overall health, the impacts of air quality on athletic performance have not been extensively investigated. Much of the previous research focused on endurance sports indicates that air quality negatively impacts athletic performance; however, the effects of air quality on non-endurance elite team performance remains largely unknown. The purpose of this study was to examine the impact of air quality on errors committed by Major League Baseball (MLB) teams, interceptions thrown by quarterbacks in the National Football League (NFL), and overall quarterback performance in the NFL. Linear regression analysis was used to determine the impact of the median air quality index (AQI) of counties with MLB and NFL teams on errors, interceptions, and overall quarterback performance of players on those MLB and NFL teams. AQI was a significant positive predictor of errors and interceptions, indicating increased errors and interceptions with decreased air quality. Similarly, quarterback performance was significantly reduced for quarterbacks from teams in counties with worse air quality. These findings suggest that air quality has a significant impact on performance in the MLB and NFL, indicating impairments in physical and cognitive performance in professional athletes when competing in areas with poorer air quality. Hence, it is likely that air quality impacts athletic performance in numerous sports that have not yet been investigated.

Virtual delivery: a panacea for the financial and ethical challenges associated with physiology laboratory classes?

There has been a gradual shift in the delivery of physiology laboratory classes over the last 30 years. For many, wet-lab demonstrations using animal tissues have been reduced or replaced with student-led investigations where students are both subjects and researchers. Despite these changes, expectations remain that physiology courses should include a practical component to encourage deeper and higher-order learning. Wet-lab tissue experiments and student-based group research formats can be expensive to run, associated with various ethical constraints, and, as discovered in these times of COVID-19, difficult to operate while adhering to physical distancing. We address the proposition that online and/or remote delivery of laboratory classes using digital technologies may provide a solution to both financial and ethical constraints of on-campus laboratory classes. Our discussions, as an international group of 10 physiologists from the United States, the United Kingdom, Canada, and Australia, revealed that although some of the financial and ethical constraints of using animal tissues and student-led investigations were addressed by the introduction of online alternatives, the construction and maintenance of online delivery modes could also be expensive and ethical issues, not previously considered, included digital equity and student data security. There was also a collective perception that if face-to-face laboratory classes were changed to an entirely virtual mode there was a risk that some intended learning outcomes would not be met. It was concluded that the "ideal" approach is likely a hybrid model whereby student attendance in face-to-face, on-campus classes is supported with interactive digital content either developed in house or obtained through third-party providers.

The clinical management of orthodontically-induced external root resorption: A questionnaire survey.

INTRODUCTION: With more dentists performing orthodontics, identifying and managing patients at risk or affected by orthodontically-induced external root resorption (OIERR) is paramount. METHODS: This study, conducted according to STROBE (STrengthening the Reporting of OBservational studies in Epidemiology), studied Australian orthodontists. Orthodontists were asked to complete a clinical questionnaire evaluating their diagnostic and management approaches to OIERR. RESULTS: Orthodontists most commonly use a history of previous root resorption and the use of an orthopantomogram to screen and monitor patients. An orthopantomogram is used either 6 months for those identified as at risk of OIERR or 10-12 months for those who are not. Once detected, most orthodontists will record OIERR in terms of severity. If severe root resorption was detected, orthodontists would compromise on the treatment outcome and promptly complete treatment; if extraction sites remain closed, most orthodontists will interrupt treatment for 3-6 months. After treatment, orthodontists' retention protocol is unchanged regardless of OIERR experience. Treatment planning for patients with generalized OIERR before treatment (P = 0.002) was the only decision shown to be associated with years of clinical experience (P >0.05). CONCLUSIONS: It is shown that no 1 method for managing OIERR exists, with most orthodontists arguing patient specificity to treatment modality. The various selected clinical approaches accurately reflect the current state of scientific literature on the topic.

International educators' attitudes, experiences, and recommendations after an abrupt transition to remote physiology laboratories.

The COVID-19 pandemic triggered university lockdowns, forcing physiology educators to rapidly pivot laboratories into a remote delivery format. This study documents the experiences of an international group of 10 physiology educators surrounding this transition. They wrote reflective narratives, framed by guiding questions, to answer the research question: "What were the changes to physiology laboratories in response to the COVID-19 pandemic?" These narratives probed educators' attitudes toward virtual laboratories before, during, and after the transition to remote delivery. Thematic analysis of the reflections found that before COVID-19 only a few respondents had utilized virtual laboratories and most felt that virtual laboratories could not replace the in-person laboratory experience. In response to university lockdowns, most respondents transitioned from traditional labs to remote formats within a week or less. The most common remote delivery formats were commercially available online physiology laboratories, homemade videos, and sample experimental data. The main challenges associated with the rapid remote transition included workload and expertise constraints, disparities in online access and workspaces, issues with academic integrity, educator and student stress, changes in learning outcomes, and reduced engagement. However, the experience generated opportunities including exploration of unfamiliar technologies, new collaborations, and revisiting the physiology laboratory curriculum and structure. Most of the respondents reported planning on retaining some aspects of the remote laboratories postpandemic, particularly with a blended model of remote and on-campus laboratories. This study concludes with recommendations for physiology educators as to how they can successfully develop and deliver remote laboratories.

Machine learning of biomarkers and clinical observation to predict eosinophilic chronic rhinosinusitis: a pilot study.

BACKGROUND: Subtyping chronic rhinosinusitis (CRS) by tissue eosinophilia has prognostic and therapeutic implications, and is difficult to predict using peripheral eosinophil counts or polyp status alone. The objective of this study was to test machine learning for prediction of eosinophilic CRS (eCRS). METHODS: Input variables were defined as peripheral eosinophil count, urinary leukotriene E4 (uLTE4) level, and polyp status. The output was diagnosis of eCRS, defined as tissue eosinophil count >10 per high-power field. Patients undergoing surgery for CRS were retrospectively reviewed for complete datasets. Univariate analysis was performed for each input as a predictor of eCRS. Logistic regression and artificial neural network (ANN) machine learning models were developed using random and surgeon-specific training/test datasets. RESULTS: A total of 80 patients met inclusion criteria. In univariate analysis, area under the receiver operator characteristic curve (AUC) for peripheral eosinophil count and uLTE4 were 0.738 (95% confidence interval [CI], 0.616 to 0.840) and 0.728 (95% CI, 0.605 to 0.822), respectively. Presence of polyps was 94.1% sensitive, but 51.7% specific. Logistic regression models using random and surgeon specific datasets resulted in AUC of 0.882 (95% CI, 0.665 to 0.970) and 0.945 (95% CI, 0.755 to 0.995), respectively. ANN models resulted in AUC of 0.918 (95% CI, 0.756 to 0.975) and 0.956 (95% CI, 0.828 to 0.999) using random and surgeon-specific datasets, respectively. Model comparison of logistic regression and ANN was not statistically different. All machine learning models had AUC greater than univariate analyses (all p < 0.003). CONCLUSION: Machine learning of 3 clinical inputs has the potential to predict eCRS with high sensitivity and specificity in this patient population. Prospective investigation using larger and more diverse populations is warranted.

Gauging the efficacy of neoadjuvant endocrine therapy in breast cancer patients with known axillary disease.

BACKGROUND AND OBJECTIVES: Neoadjuvant endocrine therapy (NET) for ER+ breast cancer can downstage primary tumors. We evaluated NET efficacy in node-positive patients. METHODS: Node-positive patients undergoing NET for ER+ breast cancer from 2012 to 2019 were reviewed. Primary endpoints included rates of axillary lymphadenectomy (ALND), pathologic complete response (pCR), and final nodal staging. RESULTS: Thirty-nine patients were included. Before NET, all were clinically node-positive (cN1 = 36, 94%; cN2 = 2, 5%; cN3 = 1, 3%; Stage II = 23, 59%, Stage III = 16, 41%). After NET, nine (23%) had clinically persistent axillary disease necessitating ALND. The remaining 30 (77%) underwent sentinel lymph node biopsy (SLNB). Of these, 25 (83%) were SLNB+ on frozen section, undergoing immediate ALND. Five patients were negative on frozen section: one had a confirmed axillary pCR, and four had residual nodal disease on permanent pathology. One underwent delayed ALND, and for the remaining three patients, decision was made to forgo ALND. Final overall axillary staging was: N0 (pCR) = 1, 3%, pN1mic = 1, 3%, pN1 = 20, 51%, pN2 = 12, 30%, pN3 = 5, 13%; Stage II = 16, 41%, Stage III = 23, 59%. CONCLUSIONS: While NET is reported to downstage primary tumors, downstaging of the axilla was unsuccessful in the majority of patients.

Alloplastic Auricular Reconstruction: Review of Implant Types, Adverse Events, and Aesthetic Outcomes.

IMPORTANCE: Alloplastic implants have been applied successfully in reconstruction of the external ear, either for congenital microtia or traumatic injury. OBJECTIVE: The objective of this study was to conduct a comprehensive systematic review of alloplastic implant materials utilized in the reconstruction of the external ear stratified by indication, specific implant type, postoperative complications, and aesthetic outcomes. EVIDENCE REVIEW: A comprehensive systematic review of published literature on alloplastic external ear reconstruction data was conducted utilizing Medline/PubMed database without timeframe limitations in June 2019. Articles were stratified by (1) indication (microtia versus trauma reconstruction) and (2) implant material type. All postoperative complications were recorded and comparatively analyzed between implant types. Aesthetic outcomes were also identified and compared between implant types. FINDINGS: A total of 755 patients (14 case series; follow-up range = 3 months--10 years) met the criteria for this study. Overall complication rate was 12.05% across all indications and materials used. The most frequent complications reported were graft exposure (7.8%), graft explantation (1.72%), and wound dehiscence (0.8%). Of the patients requiring graft explantation (n = 13), 7 (53.85%) received Medpor implants, and the other 6 (46.15%) were identified in silicone implants. Infection was only reported in Medpor implants. The overall rate of an acceptable aesthetic outcome was 99.34%. CONCLUSIONS AND RELEVANCE: Alloplastic implants are a reliable means of achieving an acceptable complication profile in external ear reconstruction. While there was an overall high rate of acceptable aesthetic outcomes, the studies evaluated in this systematic review differed in their criteria for final evaluation of aesthetic outcomes.

Effects of core temperature, skin temperature, and inter-beat interval on resting metabolic rate measurements in thermoneutral conditions.

It is important to identify potential underlying factors that can affect the variability of resting metabolic rate (RMR) measurements. The RMRs of 20 college-aged men were tested twice in stable environmental conditions, with each measurement separated by 40 min. Skin temperature, core temperature, and inter-beat interval were monitored throughout the study as identified factors that could affect RMR measurements. Since environmental conditions in a clinic or laboratory can vary, skin temperature and core temperature can be affected which may affect RMR. Similarly, prior physical activity, stress, sleep, and caffeine intake can affect inter-beat interval and may be a co-variable affecting RMR. Higher RMR measurements were compared to lower RMR measurements. RMR for the higher trial was 2068 ±â€¯66 kcal/day, the lower trial was 1975 ±â€¯65 kcal/day (t = 4.23; p < 0.01). Core temperature for higher trial was 37.1 ±â€¯0.1 °C, the lower trial was 36.8 ±â€¯0.1 °C (s = 105.00; p < 0.01). Skin temperature measurements were significantly different for the anterior bicep site (t = -2.52; p = 0.02), but not for any other site. Inter-beat interval for the higher measurement was 1038 ±â€¯33 ms, the lower measurement was 998 ±â€¯32 ms (t = 3.82; p < 0.01). However, regression analysis found that none of the variables were significant predictors for the higher RMR, lower RMR, or change in RMR. While the factors affecting RMR measurement variability remain unclear, the results suggest that typical fluctuations in core temperature, skin temperature, and inter-beat interval do not effectively predict changes in RMR in a thermoneutral environment.

Orthodontic mechanotherapies and their influence on external root resorption: A systematic review.

INTRODUCTION: This systematic review assesses the literature regarding the association between orthodontic tooth movement and external root resorption. By determining the evidence level supporting the association, the results could provide clinical evidence for minimizing the deleterious effect of orthodontic tooth movement. METHODS: Electronic databases, including MEDLINE, PubMed, Embase, Scopus, CINAHL, Cochrane Library, and LILACS, were searched up to February 2018, with hand searching of selected orthodontic journals undertaken to identify any preelectronic publications. Searches were undertaken with no restrictions on year, publication status, or language. Selection criteria included randomized controlled trials conducted with the use of fixed orthodontic appliances or sequential thermoplastic aligners on human patients. The quality of included studies was assessed with the use of the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Inter-rater agreement of the review authors was used for the inclusion of primary articles, risk of bias assessment, and evaluation of the quality of evidence (GRADE), and it was calculated with the use of the Cohen kappa statistic. RESULTS: A total of 654 articles were retrieved in the initial search. After the review process, 25 articles describing 24 individual trials met the inclusion criteria. Sample sizes ranged from 6 to 154 patients. Most articles were classified as having unclear risks of bias and very low to low quality of evidence. CONCLUSIONS: There is very low to low evidence for supporting positive associations between root resorption and increased force levels, force continuity, intrusive forces, and treatment duration. Moreover, by including a pause in treatment for patients experiencing root resorption, it may be possible for the clinician to reduce the severity of the condition. Of the included studies, the most common methodologic flaws include the absence of a control group, appropriate randomization strategy, and adequate examinations before and after treatment.

Endocytosis and degradative sorting of NMDA receptors by conserved membrane-proximal signals.

Regulation of the abundance of NMDA receptors (NMDARs) at excitatory synapses is critical during changes in synaptic efficacy underlying learning and memory as well as during synapse formation throughout neural development. However, the molecular signals that govern NMDAR delivery, maintenance, and internalization remain unclear. In this study, we identify a conserved family of membrane-proximal endocytic signals, two within the NMDAR type 1 (NR1) subunit and one within the NR2A and NR2B subunits, necessary and sufficient to drive the internalization of NMDARs. These endocytic motifs reside in the region of NMDAR subunits immediately after the fourth membrane segment, a region implicated in use-dependent rundown and NMDA channel inactivation. Although endocytosis driven by the distal C-terminal domain of NR2B is followed by rapid recycling, internalization mediated by membrane-proximal motifs selectively targets receptors to late endosomes and accelerates degradation. These results define a novel conserved signature of NMDARs regulating internalization and postendocytic trafficking.

Biomechanical study of lumbar pedicle screws in a corpectomy model assessing significance of screw height.

BACKGROUND: We tested the hypothesis that a pedicle screw construct's height is an important factor in strengthening a screw-rod system. METHODS: Six corpectomy constructs were made, each using two ultra-high-molecular-weight polyethylene blocks, 6.5-mm pedicle screws, and two 6.35-mm rods. Pedicle screws were placed at +10-, +5-, 0-, and -5-mm depths in relation to the dorsal surface of the corpectomy model. Nondestructive testing was performed in flexion/extension and in torsion. RESULTS: For all modes tested, the screw-rod constructs continued to increase in stiffness as the height of the construct was lowered, and this was statistically significant at all heights tested (P < 0.001). The stiffness increased 232% when comparing flexion at +10 and -5 mm and increased 231% in extension from +10 to -5 mm. The torsional stiffness increased 171% when comparing +10 and -5 mm. CONCLUSIONS: Thus, lower-profile instrumentation systems should be used to take advantage of this by decreasing the size and bulkiness of the implants while increasing the strength of the construct.

Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics.

The protein composition of the neuronal plasma membrane is regulated by clathrin-mediated endocytosis and changes drastically over the neuronal lifespan. Here, we utilize the transition out of the period of early postnatal growth as a model system to study age-related changes in endocytosis. Previously, we have found that the dynamic behavior of endocytic clathrin coats in dendrites changes during this period, and that clathrin coat lifetime increases in older neurons. In this study, we examine endocytosis in neuronal dendrites by measuring transferrin (Tf) uptake, and find that it is markedly reduced in older neurons in culture. This decrease was not due to a reduction in transferrin receptor protein levels, nor to a decrease in the expression of endocytic proteins. However, imaging of endocytosis in living dendrites demonstrated that cargo transport through clathrin-coated pits was slower during internalization. Thus, endocytic function in dendrites is altered in older neurons, suggesting that as neurons age, protein trafficking mechanisms are controlled to complement maturational requirements.

Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors.

Activity-dependent targeting of NMDA receptors (NMDARs) is a key feature of synapse formation and plasticity. Although mechanisms for rapid trafficking of glutamate receptors have been identified, the molecular events underlying chronic accumulation or loss of synaptic NMDARs have remained unclear. Here we demonstrate that activity controls NMDAR synaptic accumulation by regulating forward trafficking at the endoplasmic reticulum (ER). ER export is accelerated by the alternatively spliced C2' domain of the NR1 subunit and slowed by the C2 splice cassette. This mRNA splicing event at the C2/C2' site is activity dependent, with C2' variants predominating upon activity blockade and C2 variants abundant with increased activity. The switch to C2' accelerates NMDAR forward trafficking by enhancing recruitment of nascent NMDARs to ER exit sites via binding of a divaline motif within C2' to COPII coats. These results define a novel pathway underlying activity-dependent targeting of glutamate receptors, providing an unexpected mechanistic link between activity, mRNA splicing, and membrane trafficking during excitatory synapse modification.

Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors.

Endoplasmic reticulum (ER) retention mediated by the RXR (Arg-X-Arg) motif is an important quality control mechanism used by G-protein coupled receptors and ion channels, including N-methyl-D-aspartate (NMDA) receptors, to ensure the proper assembly and trafficking of multimeric complexes. During assembly, RXR motifs are masked by intersubunit interactions thereby allowing ER release. Here, we find that PKA and PKC phosphorylation sites flanking the RXR motif of the NMDA receptor NR1 subunit suppress ER retention and regulate receptor forward trafficking. These sites are differentially phosphorylated during the trafficking of NR1 subunits in vivo, and phosphorylation at these sites occurs in early secretory compartments. In addition, residues near the RXR motif not involved in phosphorylation are also required for ER retention. These results indicate that ER retention of NMDA receptors is tightly regulated, and suggest that coordinated phosphorylation by PKA and PKC mediates release of receptors from the ER for subsequent traffic to synapses. Phosphorylation-induced ER export of RXR-containing channels and receptors may serve as a novel quality control mechanism for creating a readily releasable pool of receptors sensitive to the activation of intracellular signaling pathways.

Bicondylar tibial plateau fractures: a biomechanical study.

The optimal treatment of bicondylar tibial plateau fractures remains controversial. The current study was designed to answer the following questions: (1) can a lateral fixed angle plate provide similar construct stability to dual plating techniques and (2) does the size of the medial buttress plate used in dual plating techniques have an effect on construct stability? Bicondylar tibial plateau fractures were created, reduced, and instrumented in a matched pair design using a cadaveric simulated bicondylar tibial plateau fracture model. Tibias were instrumented with one of three constructs: a lateral periarticular plate and posteromedial small fragment dynamic compression plate, a lateral periarticular plate and posteromedial (1/3)-tubular plate, or a lateral fixed angle plate. Biomechanical testing was done to determine construct stiffness, maximum load to failure, and medial condylar displacement for each of the three constructs. There was no significant difference measured between the two dual plating constructs and the lateral fixed angle plate for overall construct stiffness or with respect to medial condylar fragment displacement. A lateral fixed angle plate may have clinical applications in the treatment of bicondylar tibial plateau fractures.

Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines.

Endocytosis is a fundamental mechanism by which neurons control intercellular signaling, nutrient uptake, and synaptic transmission. This process is carried out by the assembly of clathrin coats and the budding of clathrin-coated vesicles from the neuronal plasma membrane. Here, we demonstrate that in young neurons, clathrin assembly and disassembly occur rapidly, locally, and repeatedly at "hot spots" throughout dendrites and at the tips of dendritic filopodia. In contrast, clathrin coats in mature dendrites reside in stable, long-lasting zones at sites of endocytosis, where clathrin undergoes continuous exchange with local cytosolic pools. In dendritic spines, endocytic zones lie lateral to the postsynaptic density (PSD) where they develop and persist independent of synaptic activity, akin to the PSD itself. These results reveal the presence of a novel specialization dedicated to endocytosis near the postsynaptic membrane.