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1.
Mikrochim Acta ; 191(5): 231, 2024 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-38565795

RESUMEN

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.


Asunto(s)
Medicamentos Herbarios Chinos , Animales , Dinoprost , Retroalimentación , Nitrógeno , Porosidad , Compuestos Orgánicos , Biomarcadores
2.
J Cell Mol Med ; 28(8): e18201, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38568078

RESUMEN

Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/ß-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/ß-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.


Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Osteogénesis/genética , Semaforina-3A/genética , Retroalimentación , beta Catenina , Ganglios Espinales , Neuropilina-1/genética
3.
Chaos ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38572947

RESUMEN

Feedback loops between strategies and the environment are commonly observed in socio-ecological, evolution-ecological, and psychology-economic systems. However, the impact of mutations in these feedback processes is often overlooked. This study proposes a novel model that integrates the public goods game with environmental feedback, considering the presence of mutations. In our model, the enhancement factor of the public goods game combines positive and negative incentives from the environment. By employing replicator-mutator (RM) equations, we provide an objective understanding of the system's evolutionary state, focusing on identifying conditions that foster cooperation and prevent the tragedy of the commons. Specifically, mutations play a crucial role in the RM dynamics, leading to the emergence of an oscillatory tragedy of the commons. By verifying the Hopf bifurcation condition, we establish the existence of a stable limit cycle, providing valuable insights into sustained oscillation strategies. Moreover, the feedback mechanism inherent in the public goods game model offers a fresh perspective on effectively addressing the classic dilemma of the tragedy of the commons.


Asunto(s)
Conducta Cooperativa , Teoría del Juego , Retroalimentación , Evolución Biológica , Mutación
4.
Front Public Health ; 12: 1324940, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596515

RESUMEN

Background: Adverse events in the primary care setting result in a direct cost equivalent to at least 2.5% of total healthcare spending. Across OECD countries, they lead to more than seven million avoidable hospital admissions annually. In this manuscript, we describe the protocol of a trial aimed at evaluating the effectiveness of SinergiAPS (a patient-centered audit and feedback intervention) in reducing avoidable hospital admission and explore the factors that may affect its implementation. Methods: We will conduct a 24-month, parallel, open-label, multicenter, pragmatic, hybrid type 1 randomized clinical trial. 118 primary healthcare centers with wide geographical distribution in Spain will be randomly assigned (ratio 1:1) to two groups. The intervention group will receive two audits (baseline and intermediate at 12 months) based on information collected through the administration of the PREOS-PC questionnaire (a measure of patient-reported patient safety) to a convenience sample of 100 patients per center. The intervention group will receive reports on the results of both audits, along with educational resources aimed at facilitating the design and implementation of safety improvement plans. The control group will receive care as usual. The primary outcome will be the rate of avoidable hospitalizations (administrative data). Secondary outcomes: patient-reported patient safety experiences and outcomes (PREOS-PC questionnaire); patient safety culture as perceived by professionals (MOSPSC questionnaire); adverse events reported by healthcare professionals (ad hoc questionnaire); the number of safety improvement actions which the re has implemented (ad hoc questionnaire). Outcome data will be collected at baseline and 24 months follow-up. For the evaluation of the implementation of the SinergiAPS intervention, we will draw on the Consolidated Framework for Implementation Research (CFIR). We will collect and analyze qualitative and quantitative data (30 individual interviews, implementation logbooks; questionnaires for professionals from intervention centers, and level of use of the SinergiAPS web tool). Discussion: This study will expand the scarce body of evidence existing regarding the effects and implementation of interventions aimed at promoting patient and family engagement in primary healthcare, specifically for enhancing patient safety. The study has the potential to produce an impact on clinical practice, healthcare systems, and population health.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05958108?term=sinergiAPS&rank=1 (NCT05958108).


Asunto(s)
Seguridad del Paciente , Pacientes , Humanos , España , Retroalimentación , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
5.
PLoS One ; 19(4): e0300205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38598479

RESUMEN

BACKGROUND: Feedback in residency is a necessity for progression toward clinical competency and is included in The Accreditation Council for Graduate Medical Education (ACGME) milestones as an essential component for accreditation. PURPOSE: Our study elucidates perceptions of feedback of first-year residents and aims to identify how these perceptions change after education on building expertise through deliberate practice. METHODS: First-year internal medicine and neurology residents of a mid-sized university-affiliated residency program answered a five-question 5-point unipolar response scale questionnaire regarding feedback perceptions before and after attending a workshop about building expertise through effective feedback during residency orientation. Related-Samples Wilcoxon Signed Rank Test was applied for comparing pre- versus post-questionnaire data. RESULTS: Of 31 first-year residents, 29 completed the pre-questionnaire for a completion rate of 93.5%, while 24 of 31 completed the post-questionnaire for a completion rate of 77.4%. Of the five questions, three improved when comparing pre and post responses to, including the questions on confidence in the ability to procure feedback (p = <0.001), the effort put into procuring feedback (p = 0.001), and frequency of seeking feedback (p = 0.002). Interest in receiving feedback and the importance of feedback remained unchanged after workshop attendance. CONCLUSION: Residents should be educated on building expertise through deliberate practice and how to obtain high-quality feedback, given the emphasis and essentiality of feedback within the milestone assessment system and the core competencies of ACGME. In our study, education on these topics led to significant improvement in resident perceptions of confidence in the ability to procure feedback, effort put into procuring feedback, and frequency at which feedback would be sought.


Asunto(s)
Internado y Residencia , Humanos , Retroalimentación , Educación de Postgrado en Medicina , Competencia Clínica , Acreditación , Encuestas y Cuestionarios
6.
BMC Med Educ ; 24(1): 424, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641609

RESUMEN

BACKGROUND: Feedback is a critical component of the learning process in a clinical setting. This study aims to explore medical residents' perspectives on feedback delivery and identify potential barriers to feedback-seeking in clinical training. METHODS: This cross-sectional study involved 180 medical residents across seventeen specialties. We employed the validated Residency Education Feedback Level Evaluation in Clinical Training (REFLECT) tool to assess residents' perspectives on their attitude toward feedback, quality of feedback, perceived importance, and reaction to feedback. Additionally, we explored barriers to feedback-seeking behavior among medical residents. RESULTS: The majority of medical residents held positive attitudes toward feedback. They agreed that feedback improves their clinical performance (77.7%), professional behavior (67.2%), and academic motivation (56.7%), while also influencing them to become a better specialist in their future career (72.8%). However, the study revealed critical deficiencies in the feedback process. Only 25.6% of residents reported receiving regular feedback and less than half reported that feedback was consistently delivered at suitable times and locations, was sufficiently clear or included actionable plans for improvement. A minority (32.2%) agreed that faculty had sufficient skills to deliver feedback effectively. Moreover, peer-to-peer feedback appeared to be a primary source of feedback among residents. Negative feedback, though necessary, often triggered feelings of stress, embarrassment, or humiliation. Notably, there were no significant differences in feedback perceptions among different specialties. The absence of a feedback-seeking culture emerged as a central barrier to feedback-seeking behavior in the clinical setting. CONCLUSIONS: Establishing shared expectations and promoting a culture of feedback-seeking could bridge the gap between residents' perceptions and faculty feedback delivery. Furthermore, recognizing the role of senior and peer residents as valuable feedback sources can contribute to more effective feedback processes in clinical training, ultimately benefiting resident development and patient care.


Asunto(s)
Internado y Residencia , Humanos , Estudios Transversales , Retroalimentación , Motivación , Grupo Paritario , Competencia Clínica
7.
Cell Mol Biol Lett ; 29(1): 56, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643083

RESUMEN

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.


Asunto(s)
Cuernos de Venado , MicroARNs , Animales , Humanos , Condrogénesis/genética , Retroalimentación , Cartílago/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Diferenciación Celular/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo
8.
PLoS One ; 19(4): e0302180, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635568

RESUMEN

Based on the behavioral theory of the firm, we research how performance feedback influences the formation of CEOs' passion. We articulate that previous performance directly increases CEOs' passion. Specifically, positive affective outcomes (performance above aspiration-level) advance CEOs' positive feelings and motivation toward the domains of success (obsessive passion). For instance, when a firm accomplishes performance objectives, such as reaching sales goals, CEOs' positive feelings toward developing current products would be boosted. Moreover, negative affective outcomes (performance below aspiration-level) would also positively impact CEOs' passion since the CEOs would endeavor to reduce the difference between performance and their aspiration-level. As such, performance feedback is a critical antecedent of CEOs' obsessive passion. In addition, we apply human capital as a moderator between performance feedback and CEOs' obsessive passion. Results based on multiphase survey data from 189 CEOs of Korean small- and medium-sized enterprises indicate that both positive and negative performance feedback positively increase CEOs' obsessive passion. Moreover, human capital negatively moderates the relationship between positive performance feedback and CEOs' obsessive passion and positively moderates the relationship between negative performance feedback and CEOs' obsessive passion.


Asunto(s)
Emociones , Motivación , Humanos , Retroalimentación , Logro , Ocupaciones
9.
Med Educ Online ; 29(1): 2336332, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38560892

RESUMEN

BACKGROUND: The scholarship of teaching and learning (SoTL) is a field of academic research that focuses on improving learning through reflective and informed teaching. Currently, most SoTL-related work is faculty-driven; however, student involvement in SoTL has been shown to benefit both learners and educators. Our study aims to develop a framework for increasing medical students' interest, confidence, and engagement in SoTL. METHODS: A student-led SoTL interest group was developed and a year-round program of SoTL was designed and delivered by student leaders of the group under the guidance of a faculty advisor. Individual post-session surveys were administered to evaluate participants' perceptions of each session. Pre- and post-program surveys were administered to evaluate the program impact. RESULTS: The year-round SoTL program consistently attracted the participation of medical students and faculty. Survey responses indicated strong medical student interest in the program and positive impact of the program. Increased interest and confidence in medical education research were reported by the student participants. The program design provided opportunities for student participants to network and receive ongoing feedback about medical education research they were interested or involved in. CONCLUSION: Our study provides insights for developing a framework that other institutions can reference and build upon to educate and engage students in SoTL.


Asunto(s)
Estudiantes de Medicina , Humanos , Becas , Aprendizaje , Docentes , Retroalimentación , Enseñanza , Curriculum
10.
Nat Commun ; 15(1): 2825, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561362

RESUMEN

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.


Asunto(s)
Dioxigenasas , Leptina , Animales , Humanos , Masculino , Ratones , Adipocitos/metabolismo , Peso Corporal , Dioxigenasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Retroalimentación , Leptina/metabolismo , Mamíferos/metabolismo , Obesidad/genética , Obesidad/metabolismo
11.
Physiol Plant ; 176(2): e14277, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566271

RESUMEN

In order to maintain the dynamic physiological balance, plants are compelled to adjust their energy metabolism and signal transduction to cope with the abiotic stresses caused by complex and changeable environments. The diterpenoid natural compound and secondary metabolites, sclareol, derived from Salvia sclarea, has gained significant attention owing to its economic value as a spice material and diverse physiological activities. Here, we focused on the roles and regulatory mechanisms of the sclareol diterpene synthase gene SsdTPS in the resistance of S. sclarea to abiotic stresses. Our results suggested that abiotic stresses could induce the response and upregulation of SsdTPS expression and isoprenoid pathway in S. sclarea. Ectopic expression of SsdTPS conferred drought tolerance in transgenic Arabidopsis, compared with wild-type. Overexpression of SsdTPS enhanced the transcription of ABA signal transduction synthetic regulators and induced the positive feedback upregulating key regulatory genes in the MEP pathway, thereby promoting the increase of ABA content and improving drought tolerance in transgenic plants. In addition, SsdTPS-overexpressed transgenic Arabidopsis improved the responses of stomatal regulatory genes and ROS scavenging enzyme activities and gene expression to drought stress. This promoted the stomatal closure and ROS reduction, thus enhancing water retention capacity and reducing oxidative stress damage. These findings unveil the potentially positive role of SsdTPS in orchestrating multiple regulatory mechanisms and maintaining homeostasis for improved abiotic stress resistance in S. sclarea, providing a novel insight into strategies for promoting drought resistance and cultivating highly tolerant plants.


Asunto(s)
Arabidopsis , Diterpenos , Arabidopsis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sequías , Retroalimentación , Plantas Modificadas Genéticamente/genética , Estrés Fisiológico/genética , Terpenos , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Ácido Abscísico/farmacología
12.
J Cell Biol ; 223(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573225

RESUMEN

Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy, this material is encapsulated in double-membrane vesicles termed autophagosomes, which form from precursors referred to as phagophores. Phagophores grow by lipid influx from the endoplasmic reticulum into Atg9-positive compartments and local lipid synthesis provides lipids for their expansion. How phagophore nucleation and expansion are coordinated with lipid synthesis is unclear. Here, we show that Faa1, an enzyme activating fatty acids, is recruited to Atg9 vesicles by directly binding to negatively charged membranes with a preference for phosphoinositides such as PI3P and PI4P. We define the membrane-binding surface of Faa1 and show that its direct interaction with the membrane is required for its recruitment to phagophores. Furthermore, the physiological localization of Faa1 is key for its efficient catalysis and promotes phagophore expansion. Our results suggest a positive feedback loop coupling phagophore nucleation and expansion to lipid synthesis.


Asunto(s)
Autofagosomas , Ácidos Grasos , Macroautofagia , Autofagia , Ácidos Grasos/metabolismo , Retroalimentación , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo
13.
BMC Health Serv Res ; 24(1): 433, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38581009

RESUMEN

BACKGROUND: Audit and feedback (A&F) is a widely used implementation strategy to evaluate and improve medical practice. The optimal design of an A&F system is uncertain and structured process evaluations are currently lacking. This study aimed to develop and validate a questionnaire to evaluate the use of automated A&F systems. METHODS: Based on the Clinical Performance Feedback Intervention Theory (CP-FIT) and the REFLECT-52 (REassessing audit & Feedback interventions: a tooL for Evaluating Compliance with suggested besT practices) evaluation tool a questionnaire was designed for the purpose of evaluating automated A&F systems. A Rand-modified Delphi method was used to develop the process evaluation and obtain validation. Fourteen experts from different domains in primary care consented to participate and individually scored the questions on a 9-point Likert scale. Afterwards, the questions were discussed in a consensus meeting. After approval, the final questionnaire was compiled. RESULTS: A 34-question questionnaire composed of 57 items was developed and presented to the expert panel. The consensus meeting resulted in a selection of 31 questions, subdivided into 43 items. A final list of 30 questions consisting of 42 items was obtained. CONCLUSION: A questionnaire consisting of 30 questions was drawn up for the assessment and improvement of automated A&F systems, based on CP-FIT and REFLECT-52 theory and approved by experts. Next steps will be piloting and implementation of the questionnaire.


Asunto(s)
Evaluación de Procesos, Atención de Salud , Humanos , Retroalimentación , Técnica Delfos , Encuestas y Cuestionarios
14.
Ren Fail ; 46(1): 2338932, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38616174

RESUMEN

PURPOSE: This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). METHODS: USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro. RESULTS: USP25-/- mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25-/- CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro. CONCLUSION: USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25's ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation.


Asunto(s)
Autoanticuerpos , Glomerulonefritis , Nefritis , Animales , Ratones , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Células Th17 , Retroalimentación , Diferenciación Celular
15.
Nat Commun ; 15(1): 3093, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600118

RESUMEN

Sensory-motor interactions in the auditory system play an important role in vocal self-monitoring and control. These result from top-down corollary discharges, relaying predictions about vocal timing and acoustics. Recent evidence suggests such signals may be two distinct processes, one suppressing neural activity during vocalization and another enhancing sensitivity to sensory feedback, rather than a single mechanism. Single-neuron recordings have been unable to disambiguate due to overlap of motor signals with sensory inputs. Here, we sought to disentangle these processes in marmoset auditory cortex during production of multi-phrased 'twitter' vocalizations. Temporal responses revealed two timescales of vocal suppression: temporally-precise phasic suppression during phrases and sustained tonic suppression. Both components were present within individual neurons, however, phasic suppression presented broadly regardless of frequency tuning (gating), while tonic was selective for vocal frequencies and feedback (prediction). This suggests that auditory cortex is modulated by concurrent corollary discharges during vocalization, with different computational mechanisms.


Asunto(s)
Corteza Auditiva , Animales , Corteza Auditiva/fisiología , Neuronas/fisiología , Retroalimentación Sensorial/fisiología , Retroalimentación , Callithrix/fisiología , Vocalización Animal/fisiología , Percepción Auditiva/fisiología , Estimulación Acústica
16.
Front Immunol ; 15: 1368516, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601146

RESUMEN

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.


Asunto(s)
Proteína HMGB1 , Infarto del Miocardio , Ratones , Animales , Humanos , Interleucina-6/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Retroalimentación , Infarto del Miocardio/metabolismo , Macrófagos/metabolismo , Adipocitos/metabolismo
17.
Nat Commun ; 15(1): 3268, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627390

RESUMEN

Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Here, we show that odorant mixtures of increasing complexity evoke progressively denser OSN activity, yet cortical feedback activity is of similar sparsity for all stimuli. Also, representations of complex mixtures are similar in OSNs but are decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibit a sigmoidal relationship, cortical axonal responses are complex and nonmonotonic, which can be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.


Asunto(s)
Bulbo Olfatorio , Neuronas Receptoras Olfatorias , Ratones , Animales , Bulbo Olfatorio/fisiología , Retroalimentación , Neuronas Receptoras Olfatorias/fisiología , Olfato/fisiología , Odorantes
18.
BMC Public Health ; 24(1): 1059, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627716

RESUMEN

BACKGROUND: Prevalence of self-harm In England is rising, however contact with statutory services remains relatively low. There is growing recognition of the potential role voluntary, community and social enterprise sector (VCSE) organisations have in the provision of self-harm support. We aimed to explore individuals' experiences of using these services and the barriers and facilitators to accessing support. METHODS: Qualitative, online interviews with 23 adults (18+) who have accessed support from VCSE organisations for self-harm in the Yorkshire and the Humber region were undertaken. Interviews were audio recorded and transcribed verbatim. Thematic analysis was undertaken using NVivo software. RESULTS: Participants described how a lack of service flexibility and the perception that their individual needs were not being heard often made them less likely to engage with both statutory and VCSE organisations. The complexity of care pathways made it difficult for them to access appropriate support when required, as did a lack of awareness of the types of support available. Participants described how engagement was improved by services that fostered a sense of community. The delivery of peer support played a key role in creating this sense of belonging. Education and workplace settings were also viewed as key sources of support for individuals, with a lack of mental health literacy acting as a barrier to access in these environments. CONCLUSIONS: VCSE organisations can play a crucial role in the provision of support for self-harm, however, pathways into these services remain complex and links between statutory and non-statutory services need to be strengthened. The provision of peer support is viewed as a crucial component of effective support in VCSE organisations. Further supervision and training should be offered to those providing peer support to ensure that their own mental health is protected.


Asunto(s)
Salud Mental , Conducta Autodestructiva , Adulto , Humanos , Retroalimentación , Investigación Cualitativa , Inglaterra/epidemiología , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/prevención & control , Conducta Autodestructiva/psicología
19.
J Surg Educ ; 81(5): 713-721, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580499

RESUMEN

OBJECTIVE: There are few assessments of the competence and growth of surgical residents as educators. We developed and piloted an observation-based feedback tool (FT) to provide residents direct feedback during a specific teaching session, as perceived by medical students (MS). We hypothesized that residents' performance would improve with frequent, low stakes, observation-based feedback. SETTING: This prospective study took place at an academic general surgery program. PARTICIPANTS: Focus groups of MS, surgical residents, and faculty informed FT development. MS completed the FT regarding resident teaching. DESIGN: The FT utilized 5 slider-bar ratings (0 to 100) about the teaching encounter and a checklist of 16 desirable teaching behaviors. QR codes and weekly email links were distributed for 12 months (6 clerkship blocks) to promote use. Residents were sent their results after each block. A survey after each block assessed motivation for use and gathered feedback on the FT. Descriptive statistics were used for analysis (medians, IQRs). Primary measures of performance were median of the slider-bar scores and the number of teaching behaviors. RESULTS: The FT was used 111 times; 37 of 46 residents were rated by up to 65 MS. The median rating on the slider-bars was 100 and the median number of desirable teaching behaviors was 12; there were no differences based on gender or PGY level. 10 residents had 5 or more FT observations during the year. Four residents had evaluations completed in 4 or more blocks and 19 residents had evaluations completed in at least 2 blocks. Over time, 13 residents had consistent slider-bar scores, 1 resident had higher scores, and 5 residents had lower scores (defined as a more than 5-point change from initial rating). Frequency of use of the FT decreased over time (38, 32, 9, 21, 7, 5 uses per block). The post-use survey was completed by 24 MS and 19 residents. Most common reasons for usage were interest in improving surgical learning environment, giving positive feedback (MS), and improving teaching skills (residents). Most common reasons for lack of usage from residents were "I did not think I taught enough to ask for feedback," "I forgot it existed," and "I did not know it existed." CONCLUSIONS: The FT did not lead to any meaningful improvement in resident scores over the course of the year. This may be due to overall high scores, suggesting that the components of the FT may require reevaluation. Additionally, decreased utilization of the instrument over time made it challenging to assess change in performance of specific residents, likely due to lack of awareness of the FT despite frequent reminders. Successful implementation of observation-based teaching assessments may require better integration with residency or clerkship objectives.


Asunto(s)
Cirugía General , Internado y Residencia , Internado y Residencia/métodos , Proyectos Piloto , Estudios Prospectivos , Cirugía General/educación , Humanos , Masculino , Femenino , Enseñanza , Retroalimentación , Educación de Postgrado en Medicina/métodos , Retroalimentación Formativa , Competencia Clínica , Adulto , Grupos Focales , Internet
20.
BMJ Open ; 14(4): e081063, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589258

RESUMEN

OBJECTIVES: Audit and Feedback (A&F) is a widely used quality improvement (QI) intervention in healthcare. However, not all feedback is accepted by professionals. While claims-based feedback has been previously used for A&F interventions, its acceptance by medical specialists is largely unknown. This study examined medical specialists' acceptance of claims-based A&F for QI. DESIGN: Qualitative design, with focus group discussions. Transcripts were analysed using discourse analysis. SETTING AND PARTICIPANTS: A total of five online focus group discussions were conducted between April 2021 and September 2022 with 21 medical specialists from varying specialties (urology; paediatric surgery; gynaecology; vascular surgery; orthopaedics and trauma surgery) working in academic or regional hospitals in the Netherlands. RESULTS: Participants described mixed views on using claims-based A&F for QI. Arguments mentioned in favour were (1) A&F stimulates reflective learning and improvement and (2) claims-based A&F is more reliable than other A&F. Arguments in opposition were that (1) A&F is insufficient to create behavioural change; (2) A&F lacks clinically meaningful interpretation; (3) claims data are invalid for feedback on QI; (4) claims-based A&F is unreliable and (5) A&F may be misused by health insurers. Furthermore, participants described several conditions for the implementation of A&F which shape their acceptance. CONCLUSIONS: Using claims-based A&F for QI is, for some clinical topics and under certain conditions, accepted by medical specialists. Acceptance of claims-based A&F can be shaped by how A&F is implemented into clinical practice. When designing A&F for QI, it should be considered whether claims data, as the most resource-efficient data source, can be used or whether it is necessary to collect more specific data.


Asunto(s)
Medicina , Mejoramiento de la Calidad , Niño , Humanos , Grupos Focales , Retroalimentación , Atención a la Salud , Auditoría Médica
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