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Nature Cancer Oct 2023The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The...
The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown. Here, using tractable mouse models for T-NHL and primary patient samples, we demonstrate that PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A (CoA) production. In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.
Topics: Mice; Animals; Humans; Transcription Factor AP-1; Programmed Cell Death 1 Receptor; Lymphoma, T-Cell; Genes, Tumor Suppressor; Acetyl Coenzyme A; Lymphoma, T-Cell, Peripheral; Glycolysis
PubMed: 37723306
DOI: 10.1038/s43018-023-00635-7 -
Advances in Physiology Education Dec 2023This is a memoir of my experiences in learning and teaching Physiology. It begins in 1962 when I entered the University of Washington as a medical student and began...
This is a memoir of my experiences in learning and teaching Physiology. It begins in 1962 when I entered the University of Washington as a medical student and began research in a physiology laboratory, which led to a Ph.D. degree in Physiology and Biophysics to go with my M.D. degree in 1968. At this time, both groups of students participated in the same physiology course containing both lectures and laboratories. After postdoctoral research at the NIH and in Cambridge, UK, in 1973 I joined the faculty of the Department of Physiology, University of California, San Francisco where I participated in the teaching of medical students and graduate students for nearly 15 years. By this time, the teaching of medical and graduate students had largely separated. In 1987, I moved to the University of Michigan as Professor and Chair of Physiology where my role in teaching was organizational as well as participatory for the next 35 years. In this work, I compare the teaching of medical students as well as graduate students and focus on how it has changed over this 60-year period. Over this time both medical and graduate Ph.D. education have become more integrative. Medical education is now taught in organ blocks rather than courses, and I participated in organizing the teaching of the gastrointestinal block. At Michigan, there is no longer a separate medical school class in Physiology, and graduate students enter a combined, "Program in Biomedical Science" for a year before choosing a mentor and department. Teaching remains an important part of the career of academic physiologists. It is important for schools offering the Ph.D. to provide instruction and experience in teaching. The American Physiology Society has developed new programs to assist teachers and many universities have centers on learning and teaching.
Topics: Humans; Faculty; Education, Medical; Students, Medical; Education, Graduate; Mentors; Teaching; Physiology
PubMed: 37498551
DOI: 10.1152/advan.00094.2023 -
Indian Journal of Pharmacology 2023Nearly all teachers are forced into teaching and gain experience through time, but many do not feel adequately prepared for their fieldwork in their training program.... (Review)
Review
Nearly all teachers are forced into teaching and gain experience through time, but many do not feel adequately prepared for their fieldwork in their training program. Only solution which helps teachers and students is to connect theory to practice by microteaching. It is a strategy for acquiring teaching abilities on a smaller scale, in which teachers may practice previously learned skills as well as acquire new ones. The efficiency of microteaching may be predicted using feedback from participants. While preservice instructors benefit from microteaching and students themselves find it helpful, academics have not yet looked closely at the assignment itself to determine precisely what microteaching entails. As a result, this study aids in learning more about the interactional aspects of microteaching and the effect of it in both teachers and students.
Topics: Humans; Students; Teaching
PubMed: 37737079
DOI: 10.4103/ijp.ijp_912_21 -
ELife Oct 2023The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. Post-transcriptional regulation by microRNAs (miRNAs) is a key...
The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. Post-transcriptional regulation by microRNAs (miRNAs) is a key aspect of this program. Indeed, deletion of neuron-enriched miRNAs induces strong developmental phenotypes, and miRNA levels are altered in patients with neurodevelopmental disorders. However, the mechanisms used by miRNAs to instruct brain development remain largely unexplored. Here, we identified miR-218 as a critical regulator of hippocampal assembly. MiR-218 is highly expressed in the hippocampus and enriched in both excitatory principal neurons (PNs) and GABAergic inhibitory interneurons (INs). Early life inhibition of miR-218 results in an adult brain with a predisposition to seizures. Changes in gene expression in the absence of miR-218 suggest that network assembly is impaired. Indeed, we find that miR-218 inhibition results in the disruption of early depolarizing GABAergic signaling, structural defects in dendritic spines, and altered intrinsic membrane excitability. Conditional knockout of in INs, but not PNs, is sufficient to recapitulate long-term instability. Finally, de-repressing and , two miR-218 targets, phenocopies the effects on early synchronous network activity induced by miR-218 inhibition. Taken together, the data suggest that miR-218 orchestrates formative events in PNs and INs to produce stable networks.
Topics: Animals; Adult; Humans; MicroRNAs; Neurons; Hippocampus; Interneurons; Brain; Mammals
PubMed: 37862092
DOI: 10.7554/eLife.82729 -
Nature Communications Aug 2023Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell...
Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell death is pervasive during development, but its programming is little known. Here, we report that Smad nuclear interacting protein 1 (SNIP1) promotes neural progenitor cell survival and neurogenesis and is, therefore, integral to brain development. The SNIP1-depleted brain exhibits dysplasia with robust induction of caspase 9-dependent apoptosis. Mechanistically, SNIP1 regulates target genes that promote cell survival and neurogenesis, and its activities are influenced by TGFβ and NFκB signaling pathways. Further, SNIP1 facilitates the genomic occupancy of Polycomb complex PRC2 and instructs H3K27me3 turnover at target genes. Depletion of PRC2 is sufficient to reduce apoptosis and brain dysplasia and to partially restore genetic programs in the SNIP1-depleted brain in vivo. These findings suggest a loci-specific regulation of PRC2 and H3K27 marks to toggle cell survival and death in the developing brain.
Topics: Humans; Intracellular Signaling Peptides and Proteins; RNA-Binding Proteins; Signal Transduction; NF-kappa B; Hyperplasia; Brain
PubMed: 37553330
DOI: 10.1038/s41467-023-40487-4 -
Health Literacy Research and Practice Oct 2023Suboptimal provider-parent communication contributes to poor parent comprehension of pediatric discharge instructions, which can lead to adverse outcomes. Residency is a...
OBJECTIVE
Suboptimal provider-parent communication contributes to poor parent comprehension of pediatric discharge instructions, which can lead to adverse outcomes. Residency is a critical window to acquire and learn to utilize key communication skills, potentially supported by formal training programs or visual reminders. Few studies have examined resident counseling practices or predictors of counseling quality. Our objectives were to (1) examine pediatric resident counseling practices and (2) determine how formal training and presence of discharge templates with domain-specific prompts are associated with counseling.
METHODS
We conducted a cross-sectional survey of a convenience sample of residents in the American Academy of Pediatrics Section on Pediatric Trainees. Outcomes included resident self-report of frequency of (1) counseling in domains of care and (2) use of health literacy-informed counseling strategies (pictures, demonstration, Teach Back, Show Back) (6-point scales; frequent = ). Predictor variables were (1) formal discharge-related training (e.g., lectures) and (2) hospital discharge instruction template with space for individual domains. Logistic regression analyses, utilizing generalized estimating equations when appropriate to account for multiple domains (adjusting for resident gender, postgraduate year), were performed.
KEY RESULTS
Few residents ( = 317) (13.9%) reported formal training. Over 25% of residents infrequently counsel on side effects, diagnosis, and restrictions. Resident reported use of communication strategies was infrequent: drawing pictures (24.1%), demonstration (15.8%), Teach Back (36.8%), Show Back (11.4%). Designated spaces in instruction templates for individual domains were associated with frequent domain-specific counseling (adjusted odds ratio [aOR] 4.1 [95% confidence interval: 3.5-4.8]). Formal training was associated with frequent Teach Back (aOR 2.6 [1.4-5.1]) and Show Back (aOR 2.7 [1.2-6.2]).
CONCLUSIONS
Lack of formal training and designated space for domain-specific instructions are associated with suboptimal counseling at discharge by pediatric residents. Future research should focus on determining the best mechanisms for teaching trainees communication skills and optimizing written instruction templates to support verbal counseling. [].
Topics: Child; Humans; United States; Patient Discharge; Cross-Sectional Studies; Communication; Parents; Hospitals
PubMed: 37812910
DOI: 10.3928/24748307-20230918-01 -
End-of-Life Care Education as Blended Learning Approach for General Practitioners: a Scoping Review.Journal of Cancer Education : the... Oct 2023General practitioners (GPs) are critical in providing primary palliative care in the community. Apprehensions about managing a dying person at home, difficulties in... (Review)
Review
General practitioners (GPs) are critical in providing primary palliative care in the community. Apprehensions about managing a dying person at home, difficulties in goals of care discussion, limited resources and lack of palliative care education often hinder end-of-life care provision in the community. This review focused on the end-of-life care training programs accessed by GPs and sought to understand if the training programs' content and mode of delivery aligned with their preferred needs. MEDLINE, EMBASE, CINAHL, and PsycINFO were searched to identify articles published in English between 01 January 1990 and 30 September 2022. Additionally, searches were conducted using SCOPUS, the Web of Science, and the Cochrane database using free texts. The reviewers screened the titles, abstracts, and full text to identify eligible studies and extracted textual data to analyse and generate themes. Out of 5532 citations initially accessed, 17 studies were included in the review. Six themes were generated: knowledge translation, skill development, a change in attitude, self-efficacy, satisfaction, and patient outcomes. The GPs' end-of-life care knowledge, skills, attitude, self-efficacy, and patient outcomes were better when their training had a combination of small-group interactive workshops, trigger case-based reflective learning, mentor-facilitated experiential learning, web-based modules, and peer learning. The synthesis of review findings supports blended learning as a training approach for general the practitioners' end-of-life care education as it facilitates learning and patient outcomes.
Topics: Humans; General Practitioners; Learning; Problem-Based Learning; Knowledge; Terminal Care
PubMed: 37648949
DOI: 10.1007/s13187-023-02358-w -
BMC Medical Education Jul 2023Situation, background, assessment, and recommendation (SBAR) has been extensively used in clinical and nursing education. A structured communication program increases...
BACKGROUND
Situation, background, assessment, and recommendation (SBAR) has been extensively used in clinical and nursing education. A structured communication program increases effective communication, positivity, and education satisfaction during inter-professional collaboration among nursing students. This systematic review aimed to identify and synthesize evidence on the effectiveness of SBAR-based simulation training for nursing students.
METHODS
A research protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The protocol for this study was registered in PROSPERO (CRD42021234068). Eight bibliographical databases were searched for studies published between 2001 and 2021, using relevant search terms. Searches were conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials for literature in English, and DBpia, Research Information Sharing Service, Korean Studies Information Service System, and Korea Institute of Science and Technology Information for literature in Korean. After screening titles, abstracts, and full-text papers, pertinent data were extracted, and critical appraisals of the retrieved studies were performed. Data were analyzed using the framework approach, and the findings were presented in a narrative summary. The Effective Public Health Practice Project "Quality Assessment Tool for Quantitative Studies" was used to assess the quality of the included studies.
RESULTS
Twelve studies were included: 3 randomized controlled trials and 9 quasi-experimental studies. Two overarching themes were noted, namely communication clarity and critical thinking. The results of six out of 12 studies produced significant results in favor of SBAR-based simulation in terms of communication clarity. Divergent results were obtained regarding communication ability, critical thinking, confidence, learning self-efficacy, and attitude toward patient safety. The results of these studies highlight that communication clarity ultimately leads to positive results in terms of nursing students' behaviors related to patient safety.
CONCLUSIONS
This review provides a comprehensive update of the literature on the effectiveness of SBAR-based nursing simulation programs for nursing students. These programs were found to have positive learning outcomes because of clear and concise communication. Further studies on the effectiveness of various learning outcomes derived from SBAR-based programs are required.
Topics: Humans; Communication; Education, Nursing; Learning; Simulation Training; Students, Nursing
PubMed: 37452348
DOI: 10.1186/s12909-023-04495-8 -
Advances in Physiology Education Sep 2023In the field of anatomy education, the debate over the superiority of learning with or without human donors is decades long and ongoing. Arguments for or against the use... (Review)
Review
In the field of anatomy education, the debate over the superiority of learning with or without human donors is decades long and ongoing. Arguments for or against the use of human donors in anatomy education vary, depending on the healthcare discipline. Physical therapy programs have been particularly resistant to the trend away from the use of human donors. In this personal view, I present my history of anatomy education and how my perspectives on teaching and learning anatomy have changed dramatically throughout my teaching experiences. The purpose of this article is to support instructors who are creating anatomy courses for all healthcare trainees without donors, inspire those teaching with donors to incorporate other methods of instruction and evaluation, challenge educators to examine their own biases surrounding anatomy education, and provide recommendations for developing an anatomy course without human donors. Included in this article is the perspective of a practicing physical therapist who learned through human dissection and has assisted me in the development and management of the human anatomy course in our physical therapy curriculum. This article provides an overview of how to design an anatomy course without anatomical donors for doctor of physical therapy students and includes recommendations for instructors who need to reduce or eliminate anatomical donors from their anatomy curriculum.
Topics: Humans; Anatomists; Anatomy; Cadaver; Curriculum; Dissection; Education, Medical, Undergraduate; Educational Status; Learning; Students, Medical; Teaching
PubMed: 37141435
DOI: 10.1152/advan.00004.2023