67 research outputs found

    Unpacking and validating the 'integration' core concept of physiology by an Australian team

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    Consensus was reached on seven core concepts of physiology using the Delphi method, including “integration,” outlined by the descriptor “cells, tissues, organs, and organ systems interact to create and sustain life.” This core concept was unpacked by a team of 3 Australian physiology educators into hierarchical levels, identifying 5 themes and 10 subthemes, up to 1 level deep. The unpacked core concept was then circulated among 23 experienced physiology educators for comments and to rate both level of importance and level of difficulty for each theme and subtheme. Data were analyzed using a one-way ANOVA to compare between and within themes. The main theme (theme 1: the body is organized within a hierarchy of structures, from atoms to molecules, cells, tissues, organs, and organ systems) was almost universally rated as Essential. Interestingly, the main theme was also rated between Slightly Difficult to Not Difficult, which was significantly different from all other subthemes. There were two separate subsets of themes in relation to importance, with three themes rating between Essential and Important and the two other themes rating as Important. Two subsets in the difficulty of the main themes were also identified. While many core concepts can be taught concurrently, Integration requires the application of prior knowledge, with the expectation that learners should be able to apply concepts from “cell-cell communication,” “homeostasis,” and “structure and function,” before understanding the overall Integration core concept. As such, themes from the Integration core concept should be taught within the endmost semesters of a Physiology program. NEW &amp; NOTEWORTHY This article proposes the inclusion of a core concept regarding “integration” into physiology-based curricula, with the descriptor “cells, tissues, organs, and organ systems interact to create and sustain life.” This concept expands prior knowledge and applies physiological understanding to real-world scenarios and introduces contexts such as medications, diseases, and aging to the student learning experience. To comprehend the topics within the Integration core concept, students will need to apply learned material from earlier semesters.</p

    Unpacking the 'movement of substances' core concept of physiology by an Australian team

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    Australia-wide consensus was reached on seven core concepts of physiology. The “movement of substances” core concept with the descriptor “the movement of substances (ions or molecules) is a fundamental process that occurs at all levels of organization in the organism” was unpacked by a team of three Australian physiology educators from the Delphi Task Force into hierarchical levels. There were 10 themes and 23 subthemes arranged in a hierarchy, some 3 levels deep. Using a 5-point Likert scale, the unpacked core concept was then rated for level of importance for students to understand (ranging from 1 = Essential to 5 = Not Important) and level of difficulty for students (ranging from 1 = Very Difficult to 5 = Not Difficult) by the 23 physiology educators from different Australian universities, all with a broad range of teaching and curriculum experience. Survey data were analyzed using a one-way ANOVA to compare between and within concept themes. The main themes all were rated on average as important. There was a wide range of difficulty ratings and more variation for this concept compared with the other core concepts. This may in part be due to the physical forces such as gravity, electrochemistry, resistance, and thermodynamics that underpin this concept, which in themselves are inherently complex. Separation of concepts into subthemes can help prioritize learning activities and time spent on difficult concepts. Embedding of core concepts across curricula will allow commonality and consistency between programs of study and inform learning outcomes, assessment, and teaching and learning activities. NEW &amp; NOTEWORTHY This article unpacks the core concept of the “movement of substances” within the body, with the aim to produce a resource that will help guide the teaching of physiology at tertiary education institutes in Australia. The concept introduces fundamental knowledge of the factors that drive substance movement and then applies them in physiological contexts.</p

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Unpacking and validating the "physiological adaptation" core concept of physiology

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    A national Task Force of 25 Australian physiology educators used the Delphi protocol to develop seven physiology core concepts that were agreed to nationally. The aim of the current study was to unpack the "physiological adaptation" core concept with the descriptor "organisms adjust and adapt to acute and chronic changes in the internal and external environments across the lifespan." This core concept was unpacked by three Task Force members and a facilitator into four themes and nine subthemes that encompass the role of stressors and disturbed homeostasis in adaptation and the capacity for, and the nature of, the physiological adaptation. Twenty-two Task Force members then provided feedback and rated the themes and subthemes for level of importance and difficulty for students to learn via an online survey using a five-point Likert scale. Seventeen respondents completed all survey questions. For all themes/subthemes, importance was typically rated 1 (Essential) or 2 (Important) (n = 17, means ±SD ranged from 1.1 ± 0.3 to 2.2 ± 0.9), and difficulty was typically rated 3 (Moderately Difficult) (n = 17, means ranged from 2.9 ± 0.7 to 3.4 ± 0.9). Subtle differences in the proportion of importance scores (n = 17, Fisher's exact: P = 0.004, ANOVA: F12,220 = 2.630, P = 0.003; n = 22, Fisher's exact: P = 0.002, ANOVA: F12,281 = 2.743, P < 0.001), but not difficulty scores, were observed between themes/subthemes, and free-text feedback was minor. The results suggest successful unpacking of the physiological adaptation core concept. The themes and subthemes can inform the design of learning outcomes, assessment, and teaching and learning activities that have commonality and consistency across curricula.NEW &amp; NOTEWORTHY An Australian Task Force of physiology educators identified physiological adaptation as a core concept of physiology. It was subsequently unpacked into four themes and nine subthemes. These were rated, by the Task Force, Essential or Important and Moderately Difficult for students to learn. The themes and subthemes can inform the design of learning outcomes, assessments, and teaching and learning activities that have commonality and consistency across curricula.</p

    Establishing Consensus for the Core Concepts of Physiology in the Australian Higher Education Context using the Delphi Method

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    A set of core concepts ("big ideas") integral to the discipline of physiology are important for students to understand and demonstrate their capacity to apply. We found poor alignment of learning outcomes in programs with physiology majors (or equivalent) from 17 Australian universities and the 15 core concepts developed by a team in the United States. The objective of this project was to reach Australia-wide consensus on a set of core concepts for physiology, which can be embedded in curricula across Australian universities. A four-phase Delphi method was employed, starting with the assembling of a Task Force of physiology educators with extensive teaching and curriculum development expertise from 25 Australian universities. After two online meetings and a survey, the Task Force reached agreement on seven core concepts of physiology and their descriptors, which were then sent out to the physiology educator community across Australia for agreement. The seven core concepts and their associated descriptions were endorsed through this process (n = 138). In addition, embedding the core concepts across the curriculum was supported by both Task Force members (85.7%) and educators (82.1%). The seven adopted core concepts of human physiology were Cell Membrane, Cell-Cell Communication, Movement of Substances, Structure and Function, Homeostasis, Integration, and Physiological Adaptation. The core concepts were subsequently unpacked into themes and subthemes. If adopted, these core concepts will result in consistency across curricula in undergraduate physiology programs and allow for future benchmarking.NEW &amp; NOTEWORTHY This is the first time Australia-wide agreement has been reached on the core concepts of physiology with the Delphi method. Embedding of the core concepts will result in consistency in physiology curricula, improvements to teaching and learning, and benchmarking across Australian universities.</p

    Unpacking and validating the 'cell membrane' core concept of physiology by an Australian team

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    A task force of physiology educators from 25 Australian universities generated an Australia-wide consensus on seven core concepts for physiology curricula. One adopted core concept was “cell membrane,” defined as “Cell membranes determine what substances enter or leave the cell and its organelles. They are essential for cell signaling, transport, and other cellular functions.” This concept was unpacked by a team of 3 Australian physiology educators into 4 themes and 33 subthemes arranged in a hierarchical structure up to 5 levels deep. The four themes related to defining the cell membrane, cell membrane structure, transport across cell membranes, and cell membrane potentials. Subsequently, 22 physiology educators with a broad range of teaching experience reviewed and assessed the 37 themes and subthemes for importance for students to understand and the level of difficulty for students on a 5-point Likert scale. The majority (28) of items evaluated were rated as either Essential or Important. Theme 2: cell membrane structure was rated as less important than the other three themes. Theme 4: membrane potential was rated most difficult, while theme 1: defining cell membranes was rated as the easiest. The importance of cell membranes as a key aspect of biomedical education received strong support from Australian educators. The unpacking of the themes and subthemes within the cell membrane core concept provides guidance in the development of curricula and should facilitate better identification of the more challenging aspects within this core concept and help inform the time and resources required to support student learning.NEW &amp; NOTEWORTHY The “cell membrane” core concept was unpacked by a team of Australian physiology educators into a conceptual framework to provide guidance for students and educators. Key themes in the cell membrane core concept were cell membrane definition and structure, transport across cell membranes, and membrane potentials. Australian educators reviewing the framework identified cell membrane as an essential yet relatively simple core concept, suggesting that this is well-placed in foundational physiology courses across a diverse range of degrees.</p

    Population genomics of the critically endangered kākāpō

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    Summary The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species

    Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target

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    Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain
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