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1.
Artículo en Inglés | MEDLINE | ID: mdl-39028318

RESUMEN

INTRODUCTION: Improving health care quality and patient safety are top priorities for the medical field. Robust continuing medical education (CME) programs represent major interventions to effectively teach quality improvement (QI) principles to practicing physicians. In particular, eLearning, a term describing online and distance learning interventions using digital tools, provides a means for CME interventions to reach broader audiences. Although there has been a focus on CME addressing QI, no knowledge synthesis has focused specifically on eLearning interventions. The purpose of this review was to examine the current landscape of eLearning interventions in QI-focused CME. METHODS: We conducted a scoping review using the framework developed by Arksey and O'Malley as revised by Levac. We searched five databases and identified 2467 prospective publications, which two authors independently screened for inclusion. From each included article, two authors independently extracted data on the instructional modalities and QI tools used and met regularly to achieve consensus. RESULTS: Twenty-one studies were included. Most studies used blended instruction (n = 12) rather than solely eLearning interventions. Salient findings included the importance of coaching from QI experts and institutional support for planning and implementing eLearning interventions. Lack of protected time and resources for participants were identified as barriers to participation in CME activities, with small practices being disproportionately affected. DISCUSSION: Partnerships between CME developers and sponsoring organizations are vital in creating sustainable eLearning interventions for QI-focused CME. Remote coaching can be an effective strategy to provide ongoing support to geographically separated learners.

2.
J Craniofac Surg ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028179

RESUMEN

The use of porcine-derived collagen membranes (PDCM) to improve intraoral soft tissue rehabilitation remains under investigation. Different degrees of crosslinking have yielded differences in resorption time and inflammation surrounding collagen membranes. The aim of this study was to evaluate the in vivo performance of bilayered PDCMs with varying degrees of crosslinking for the regeneration of oral soft tissue defects. Bilateral split-thickness oral mucosa defects were created in mandibles of beagles (n=17) and assigned to one of the following: bilayer PDCM (high crosslinking porcine dermis in sheet form-H-xlink) and (low crosslinking porcine dermis in sheet form-L-xlink), bilayer PDCM (non-crosslinked predicate collagen membrane in spongy form-Ctrl), or negative control (Sham) and compared with positive control (unoperated). Animals were euthanized after 4-, 8-, or 12-weeks of healing to evaluate soft tissue regeneration and remodeling through histomorphometric analyses. H-xlink membranes presented delayed healing with a poorly developed epithelial layer (analogous to the sham group) across time points. Relative to Ctrl at 8 and 12 weeks, defects treated with H-xlink presented no difference in semiquantitative scores ( P > 0.05), while L-xlink exhibited greater healing ( P = 0.042, P = 0.043, at 8 and 12 weeks, respectively). Relative to positive control, L-xlink exhibited similar healing at 8 weeks and greater healing at 12 weeks ( P = 0.037) with a well-developed epithelial layer. Overall, groups treated with L-xlink presented with greater healing relative to the positive control after 12 weeks of healing and may serve as an alternative to autologous grafts for intraoral soft tissue regeneration.

3.
Eur J Appl Physiol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044028

RESUMEN

INTRODUCTION: Acute exercise improves cognitive performance. However, it remains unclear what triggers cognitive improvement. Electrical muscle stimulation (EMS) facilitates the examination of physiological changes derived from peripheral muscle contraction during exercise. Thus, we compared the effects of EMS and voluntary exercise at low- or moderate-intensity on reaction time (RT) in a cognitive task to understand the contribution of central and peripheral physiological factors to RT improvement. METHODS: Twenty-four young, healthy male participants performed a Go/No-Go task before and after EMS/exercise. In the EMS condition, EMS was applied to the lower limb muscles. In the low-intensity exercise condition, the participants cycled an ergometer while maintaining their heart rate (HR) at the similar level during EMS. In the moderate-intensity exercise condition, exercise intensity corresponded to ratings of perceived exertion of 13/20. The natural log-transformed root mean square of successive differences between adjacent inter-beat (R-R) intervals (LnRMSSD), which predominantly reflects parasympathetic HR modulation, was calculated before and during EMS/exercise. RESULTS: RT improved following moderate-intensity exercise (p = 0.002, Cohen' d = 0.694), but not following EMS (p = 0.107, Cohen' d = 0.342) and low-intensity exercise (p = 0.076, Cohen' d = 0.380). Repeated measures correlation analysis revealed that RT was correlated with LnRMSSD (Rrm(23) = 0.599, p = 0.002) in the moderate-intensity exercise condition. CONCLUSION: These findings suggest that the amount of central neural activity and exercise pressor reflex may be crucial for RT improvement. RT improvement following moderate-intensity exercise may, at least partly, be associated with enhanced sympathetic nervous system activity.

4.
Cancers (Basel) ; 16(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39001492

RESUMEN

Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.

5.
Front Physiol ; 15: 1408963, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827991

RESUMEN

The purpose of this study was to investigate whether a combination of electrical muscle stimulation (EMS) and cycling exercise is beneficial for improving cognitive performance. Eighteen participants (7 females and 11 males) performed a Go/No-Go task before and 2 min after i) cycling exercise (EX), ii) a combination of EMS and cycling (EMS + EX) and iii) a control (rest) intervention in a randomized controlled crossover design. In the EX intervention, the participants cycled an ergometer for 20 min with their heart rate maintained at ∼120 beats·min-1. In the EMS + EX intervention, the participants cycled an ergometer simultaneously with EMS for 20 min, with heart rate maintained at ∼120 beats·min-1. In the Control intervention, the participants remained at rest while seated on the ergometer. Cognitive performance was assessed by reaction time (RT) and accuracy. There was a significant interaction between intervention and time (p = 0.007). RT was reduced in the EX intervention (p = 0.054, matched rank biserial correlation coefficient = 0.520). In the EMS + EX intervention, RT was not altered (p = 0.243, Cohen's d = 0.285) despite no differences in heart rate between the EX and EMS + EX interventions (p = 0.551). RT was increased in the Control intervention (p = 0.038, Cohen's d = -0.529). These results indicate that combining EMS and cycling does not alter cognitive performance despite elevated heart rate, equivalent to a moderate intensity. The present findings suggest that brain activity during EMS with cycling exercise may be insufficient to improve cognitive performance when compared to exercise alone.

6.
Trends Mol Med ; 30(8): 708-712, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38719712

RESUMEN

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.


Asunto(s)
Cognición , Dopamina , Ejercicio Físico , Humanos , Cognición/fisiología , Ejercicio Físico/fisiología , Dopamina/metabolismo , Animales
7.
Clin Teach ; : e13768, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651678

RESUMEN

INTRODUCTION: Physician educators are essential in training the next generation of physicians. However, physician educators' perspectives about what experiences they find beneficial to their teaching and the prevalence of these experiences remain unknown. Guided by social cognitive career theory (SCCT) and communities of practice (CoP), we explored what experiences physician educators perceive as beneficial in preparing them to teach. METHODS: In 2019, the Uniformed Services University School of Medicine in the United States surveyed its physician alumni to understand their education experiences during medical school, their current career path and what has contributed to their teaching role. Content analysis was applied to extract themes across the text response. Chi-square analysis was applied to examine if perceived contributing factors vary based on physician educators' gender, specialty and academic ranks. RESULTS: The five most prevalent contributing factors participants (n = 781) identified are (1) experiences gained during residency and fellowship (29.8%), (2) teaching as faculty member (28.9%) and (3) class experiences and peer interaction during medical school (26%). We organised three themes that reflected major avenues of how physician educators acquire teaching skills: reflection about quality teaching, journey as learners and learning by doing. Gender and clinical specialty were differentially associated with contributing factors such as faculty development and meta-reflection. CONCLUSION: The results are in line with theories of SCCT and CoP, in which we identified self-directed learning and regulation in shaping physician educators' teaching. The findings also revealed gaps and potential contexts for more formalised teaching practices to develop physician educators.

8.
Acad Med ; 99(9): 981-986, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38619532

RESUMEN

PURPOSE: A preprint is a version of a research manuscript posted to a preprint server prior to peer review. Preprints enable authors to quickly and openly share research, afford opportunities for expedient feedback, and enable immediate listing of research on grant and promotion applications. In medical education, most journals welcome preprints, which suggests that preprints play a role in the field's discourse. Yet, little is known about medical education preprints, including author characteristics, preprint use, and ultimate publication status. This study provides an overview of preprints in medical education to better understand their role in the field's discourse. METHOD: The authors queried medRxiv, a preprint repository, to identify preprints categorized as "medical education" and downloaded related metadata. CrossRef was queried to gather information on preprints later published in journals. Data were analyzed using descriptive statistics. RESULTS: Between 2019 and 2022, 204 preprints were classified in medRxiv as "medical education," with most deposited in 2021 (n = 76; 37.3%). On average, preprint full-texts were downloaded 1,875.2 times, and all were promoted on social media. Preprints were authored, on average, by 5.9 authors. Corresponding authors were based in 41 countries, with 45.6% in the United States, the United Kingdom, and Canada. Almost half (n = 101; 49.5%) became published articles in predominantly peer-reviewed journals. Preprints appeared in 65 peer-reviewed journals, with BMC Medical Education (n = 9; 8.9%) most represented. CONCLUSIONS: Medical education research is being deposited as preprints, which are promoted, heavily accessed, and subsequently published in peer-reviewed journals, including medical education journals. Considering the benefits of preprints and the slowness of medical education publishing, it is likely that preprint depositing will increase and preprints will be integrated into the field's discourse. The authors propose next steps to facilitate responsible and effective creation and use of preprints.


Asunto(s)
Educación Médica , Publicaciones Periódicas como Asunto , Preimpresos como Asunto , Humanos , Educación Médica/tendencias , Educación Médica/métodos , Revisión de la Investigación por Pares/tendencias , Edición/tendencias , Edición/estadística & datos numéricos
9.
J Orthop Res ; 42(9): 1998-2006, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38598203

RESUMEN

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.


Asunto(s)
Becaplermina , Fosfatos de Calcio , Colágeno Tipo I , Animales , Conejos , Fosfatos de Calcio/uso terapéutico , Bovinos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/farmacología , Fracturas de la Tibia/cirugía , Fracturas no Consolidadas/tratamiento farmacológico , Factor de Crecimiento Derivado de Plaquetas/uso terapéutico , Curación de Fractura/efectos de los fármacos , Tibia , Osteogénesis/efectos de los fármacos
10.
Mod Pathol ; 37(6): 100488, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38588881

RESUMEN

Biomarker-driven therapeutic clinical trials require the implementation of standardized, evidence-based practices for sample collection. In diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target for which window-of-opportunity clinical trials could facilitate the identification of promising new agents. Yet, the relevant preanalytic variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma. First, we determined the impact of delayed time-to-formalin fixation, or cold ischemia time (CIT), on the quantitative assessment of cellular expression of 6 phosphoproteins that are readouts of PI3K/AK/mTOR activity (phosphorylated-proline-rich Akt substrate of 40 kDa (p-PRAS40, T246), -mechanistic target of rapamycin (p-mTOR; S2448); -AKT (p-AKT, S473); -ribosomal protein S6 (p-RPS6, S240/244 and S235/236), and -eukaryotic initiation factor 4E-binding protein 1 (p-4EBP1, T37/46). With CITs ≥ 2 hours, typical of routine clinical handling, all had reduced or altered expression with p-RPS6 (S240/244) exhibiting relatively greater stability. A similar pattern was observed using patient tumor samples from the operating room with p-4EBP1 more sensitive to delayed fixation than p-RPS6 (S240/244). Many clinical trials utilize unstained slides for biomarker evaluation. Thus, we evaluated the impact of slide storage conditions on the detection of p-RPS6 (S240/244), p-4EBP1, and p-AKT. After 5 months, storage at -80°C was required to preserve the expression of p-4EBP1 and p-AKT, whereas p-RPS6 (240/244) expression was not stable regardless of storage temperature. Biomarker heterogeneity impacts optimal tumor sampling. Quantification of p-RPS6 (240/244) expression in multiple regionally distinct human tumor samples from 8 patients revealed significant intratumoral heterogeneity. Thus, the accurate assessment of PI3K/AKT/mTOR signaling in diffuse glioma must overcome intratumoral heterogeneity and multiple preanalytic factors, including time-to-formalin fixation, slide storage conditions, and phosphoprotein of interest.


Asunto(s)
Neoplasias Encefálicas , Glioma , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Glioma/patología , Glioma/metabolismo , Glioma/genética , Ratones , Biomarcadores de Tumor/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Modelos Animales de Enfermedad , Manejo de Especímenes/métodos
11.
PLoS One ; 19(3): e0299475, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483945

RESUMEN

Using a prospective observational design, this study investigated the hypothesis that competing in the Suffolk Back Yard Ultra-marathon, would result in impaired cognitive performance and examined whether pre-race sleep patterns could mitigate this. Fifteen runners (1 female) volunteered to undertake this study and eleven males were included in the final analysis. Before the race and after withdrawal participants completed the following cognitive performance tasks: 2 Choice Reaction Time (2CRT), Stroop, and the Tower Puzzle. Pre-race sleep strategies were subjectively recorded with a 7-day sleep diary. Following race withdrawal, reaction time increased (Δ 77±68 ms; p = 0.004) in the 2CRT and executive function was impaired in the Stroop task (Interference score Δ -4.3±5.6 a.u.; p = 0.028). Decision making was not affected in the Tower Puzzle task. There was a significant correlation between the pre-race 7-day average sleep scores and both 2CRT Δ throughput (r = 0.61; p = 0.045) and 2CRT Δ RT (r = -0.64; p = 0.034). This study supports the hypothesis that running an ultra-marathon, which includes at least one night of sleep deprivation, impairs cognitive performance and provides novel evidence suggesting good sleep quality, in the week prior to an ultra-marathon, could minimise these effects.


Asunto(s)
Carrera de Maratón , Privación de Sueño , Femenino , Humanos , Masculino , Cognición , Esfuerzo Físico , Sueño
12.
bioRxiv ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38496403

RESUMEN

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by 'decoding' neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. Teaser: A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

14.
Acad Med ; 99(9): 1048, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38478805

RESUMEN

Bibliometric network analysis is an analytical approach that enables researchers to visualize the relationships between a set of research items (e.g., journal articles, books). There are 3 types of bibliometric network analyses, and multiple tools to conduct the analysis and visualize results (e.g., VOSviewer , 1Gephi2 ). For health professions educators, bibliometric network analysis is valuable for discovering the field's emerging trends, popular topics, and multidisciplinary relationships. 3,4.


Asunto(s)
Bibliometría , Empleos en Salud , Humanos , Empleos en Salud/educación , Investigadores/estadística & datos numéricos
15.
Sci Rep ; 14(1): 6362, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493204

RESUMEN

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.


Asunto(s)
Glioblastoma , Glioma , Humanos , Empalme Alternativo , Antígenos de Superficie , Glioma/genética , Antígenos de Histocompatibilidad , ARN , Antígenos de Neoplasias/genética , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores
16.
J Physiol ; 602(3): 461-484, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38165254

RESUMEN

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.


Asunto(s)
Dopamina , Tomografía de Emisión de Positrones , Humanos , Racloprida , Tiempo de Reacción , Tomografía de Emisión de Positrones/métodos , Ejercicio Físico , Neurotransmisores
17.
Cell ; 187(2): 446-463.e16, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38242087

RESUMEN

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Modelos Biológicos , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Epigenómica , Genómica , Glioblastoma/genética , Glioblastoma/patología , Análisis de la Célula Individual , Microambiente Tumoral , Heterogeneidad Genética
18.
J Strength Cond Res ; 38(5): 906-911, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38241463

RESUMEN

ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.


Asunto(s)
Traumatismos en Atletas , COVID-19 , Fútbol Americano , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Retrospectivos , Fútbol Americano/lesiones , Masculino , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/cirugía , Universidades , Lesiones del Hombro/epidemiología , Incidencia , Adulto Joven , SARS-CoV-2 , Traumatismos de la Rodilla/cirugía , Traumatismos de la Rodilla/epidemiología , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/epidemiología
19.
Acad Med ; 99(4): 445-451, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38266197

RESUMEN

PURPOSE: Faculty at academic health centers (AHCs) are charged with engaging in educational activities. Some faculty have developed educational value units (EVUs) to track the time and effort dedicated to these activities. Although several AHCs have adopted EVUs, there is limited description of how AHCs engage with EVU development and implementation. This study aimed to understand the collective experiences of AHCs with EVUs to illuminate benefits and barriers to their development, use, and sustainability. METHOD: Eleven faculty members based at 10 AHCs were interviewed between July and November 2022 to understand their experiences developing and implementing EVUs. Participants were asked to describe their experiences with EVUs and to reflect on benefits and barriers to their development, use, and sustainability. Transcripts were analyzed using thematic analysis. RESULTS: EVU initiatives have been designed and implemented in a variety of ways, with no AHCs engaging alike. Despite differences, the authors identified shared themes that highlighted benefits and barriers to EVU development and implementation. Within and between these themes, a series of tensions were identified in conjunction with the ways in which AHCs attempted to mitigate them. Related to barriers, the majority of participants abandoned or paused their EVU initiatives; however, no differences were identified between those AHCs that retained EVUs and those that did not. CONCLUSIONS: The collective themes identified suggest that AHCs implementing or sustaining an EVU initiative would need to balance benefits and barriers in light of their unique context. Study findings align with reviews on EVUs and provide additional nuance related to faculty motivation to engage in education and the difficulties of defining EVUs. The lack of differences observed between those AHCs that retained EVUs and those that did not suggests that EVUs may be challenging to implement because of the complexity of AHCs and their faculty.


Asunto(s)
Docentes Médicos , Facultades de Medicina , Humanos , Docentes Médicos/educación , Investigación Cualitativa , Motivación , Centros Médicos Académicos
20.
Physiol Behav ; 274: 114409, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37977251

RESUMEN

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.


Asunto(s)
Función Ejecutiva , Privación de Sueño , Femenino , Humanos , Cognición , Hipoxia , Sueño , Ejercicio Físico , Estudios Cruzados , Masculino
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