Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 115
Filtrar
1.
Artículo en Inglés | MEDLINE | ID: mdl-39073160

RESUMEN

BACKGROUND: Understanding patients' experiences accessing primary health care (PHC) is necessary to improve service organisation. This study aims to examine individual, organisational, and contextual factors associated with patients' experience of accessing the multidisciplinary PHC clinic to which they are attached. METHODS: This cross-sectional study builds on survey data collected in multidisciplinary PHC clinics located in 14 regions in the province of Quebec (Canada). Between September 2022 and June 2023, an online questionnaire was sent to patients with an email contact and attached to a family physician. Two patient-reported experience measures were assessed: (1) difficulty obtaining an appointment with their regular family physician or nurse practitioner and (2) perceived unmet healthcare needs. A self-reported online questionnaire based on the advanced access model was also sent to PHC professionals and administrative staff to assess the use of advanced access strategies in their practice. Multilevel logistic regression models were fit. Stratified analyses were conducted according to the number of consultations received. FINDINGS: In total, 122,397 patients and 847 family physicians, 97 nurse practitioners and 347 administrative staff nested into 104 clinics answered the survey. In the overall sample, having a chronic disorder was the only individual factor associated with the patient experience of access. Organizational factors including estimation of demand and supply, use of a referral algorithm, and strategies to optimise consultations were associated with a better access experience. Patients from medium size clinics compared to small clinics had better experiences of care for both outcomes. Stratified analysis indicated similar results for patients who consulted at the clinic 1-5 times in the last 12 months as observed in the overall sample. CONCLUSIONS: This study indicates that enhancing organizational processes can improve patients' access experiences.

2.
BMC Prim Care ; 25(1): 160, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730345

RESUMEN

BACKGROUND: The advanced access (AA) model is among the most recommended innovations for improving timely access in primary care (PC). AA is based on core pillars such as comprehensive planning for care needs and supply, regularly adjusting supply to demand, optimizing appointment systems, and interprofessional collaborative practices. Exposure of family medicine residents to AA within university-affiliated family medicine groups (U-FMGs) is a promising strategy to widen its dissemination and improve access. Using four AA pillars as a conceptual model, this study aimed to determine the theoretical compatibility of Quebec's university-affiliated clinics' residency programs with the key principles of AA. METHODS: A cross-sectional online survey was sent to the chief resident and academic director at each participating clinic. An overall response rate of 96% (44/46 U-FMGs) was obtained. RESULTS: No local residency program was deemed compatible with all four considered pillars. On planning for needs and supply, only one quarter of the programs were compatible with the principles of AA, owing to residents in out-of-clinic rotations often being unavailable for extended periods. On regularly adjusting supply to demand, 54% of the programs were compatible. Most (82%) programs' appointment systems were not very compatible with the AA principles, mostly because the proportion of the schedule reserved for urgent appointments was insufficient. Interprofessional collaboration opportunities in the first year of residency allowed 60% of the programs to be compatible with this pillar. CONCLUSIONS: Our study highlights the heterogeneity among local residency programs with respect to their theoretical compatibility with the key principles of AA. Future research to empirically test the hypotheses raised by this study is warranted.


Asunto(s)
Accesibilidad a los Servicios de Salud , Internado y Residencia , Quebec , Internado y Residencia/organización & administración , Estudios Transversales , Humanos , Accesibilidad a los Servicios de Salud/organización & administración , Medicina Familiar y Comunitaria/educación , Atención Primaria de Salud/organización & administración , Encuestas y Cuestionarios
3.
JACC Case Rep ; 29(8): 102304, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38774800

RESUMEN

We present a full-term neonate with a postnatal diagnosis with a left aortic arch, bilateral ducti, and discontinuous branch pulmonary arteries with right pulmonary artery arising from right duct. Upon left ductal constriction, the patient experienced coarctation of the aorta, illustrating the importance of careful and serial interrogation of rare cardiac anatomy.

4.
Qual Health Res ; : 10497323241237411, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38501324

RESUMEN

Although realist evaluation (RE) requires multiple data collection methods, qualitative interviews are considered most valuable and are most frequently used. The guiding principles of RE may limit the emergence of new Context-Mechanism-Outcome (CMO) configurations by evoking particular underlying mechanisms. This paper proposes a new method for conducting semi-structured interviews in the RE context by drawing on the literature and examining the ability of vignettes to explore perceptions about specific situations. Vignettes are developed based on researchers' knowledge of the setting and program theory and are updated through an iterative process throughout data collection. Interviews focus on situations illustrated in the vignette to capture variations in interviewees' perceptions. This method constrains interviewees to using retroduction to identify the hidden underlying mechanisms that link contextual elements to outcomes based on their experiences. This method allows researchers to focus on CMO configurations without evoking mechanisms, which contributes to the rigor of the method.

5.
Sci Rep ; 14(1): 5528, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448508

RESUMEN

Extracellular vesicles (EVs) have been implicated in metastasis and proposed as cancer biomarkers. However, heterogeneity and small size makes assessments of EVs challenging. Often, EVs are isolated from biofluids, losing spatial and temporal context and thus lacking the ability to access EVs in situ in their native microenvironment. This work examines the capabilities of label-free nonlinear optical microscopy to extract biochemical optical metrics of EVs in ex vivo tissue and EVs isolated from biofluids in cases of human breast cancer, comparing these metrics within and between EV sources. Before surgery, fresh urine and blood serum samples were obtained from human participants scheduled for breast tumor surgery (24 malignant, 6 benign) or healthy participants scheduled for breast reduction surgery (4 control). EVs were directly imaged both in intact ex vivo tissue that was removed during surgery and in samples isolated from biofluids by differential ultracentrifugation. Isolated EVs and freshly excised ex vivo breast tissue samples were imaged with custom nonlinear optical microscopes to extract single-EV optical metabolic signatures of NAD(P)H and FAD autofluorescence. Optical metrics were significantly altered in cases of malignant breast cancer in biofluid-derived EVs and intact tissue EVs compared to control samples. Specifically, urinary isolated EVs showed elevated NAD(P)H fluorescence lifetime in cases of malignant cancer, serum-derived isolated EVs showed decreased optical redox ratio in stage II cancer, but not earlier stages, and ex vivo breast tissue showed an elevated number of EVs in cases of malignant cancer. Results further indicated significant differences in the measured optical metabolic signature based on EV source (urine, serum and tissue) within individuals.


Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Vesículas Extracelulares , Humanos , Femenino , NAD , Biopsia , Mama , Microambiente Tumoral
6.
Pediatr Transplant ; 28(1): e14584, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37470130

RESUMEN

BACKGROUND: Pediatric heart transplantation (HT) continues to be limited by the shortage of donor organs, distance constraints, and the number of potential donor offers that are declined due to the presence of multiple risk factors. METHODS: We report a case of successful pediatric HT in which multiple risk factors were mitigated through a combination of innovative donor utilization improvement strategies. RESULTS: An 11-year-old, 25-kilogram child with cardiomyopathy and pulmonary hypertension, on chronic milrinone therapy and anticoagulated with apixaban, was transplanted with a heart from a Hepatitis C virus positive donor and an increased donor-to-recipient weight ratio. Due to extended geographic distance, an extracorporeal heart preservation system (TransMedics™ OCS Heart) was used for procurement. No significant bleeding was observed post-operatively, and she was discharged by post-operative day 15 with normal biventricular systolic function. Post-transplant Hepatitis C virus seroconversion was successfully treated. CONCLUSIONS: Heart transplantation in donors with multiple risk factor can be achieved with an integrative team approach and should be taken into consideration when evaluating marginal donors in order to expand the current limited donor pool in pediatric patients.


Asunto(s)
Trasplante de Corazón , Obtención de Tejidos y Órganos , Femenino , Humanos , Niño , Donantes de Tejidos , Corazón , Factores de Riesgo
7.
Prev Med Rep ; 36: 102512, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38116285

RESUMEN

Objective: To evaluate if access to team-based primary care is related to medication management outcomes for older adults. Methods: We completed two retrospective cohort studies using administrative health data for older adults (66+) in Ontario (n = 428,852) and Québec (n = 310,198) who were rostered with a family physician (FP) between the 2001/02 and 2017/18 fiscal years. We generated matched comparison groups of older adults rostered to an FP practicing in a team-based model, and older adults rostered to an FP in a non-team model. We compared the following outcomes between these groups: any adverse drug reactions (ADRs), any potentially inappropriate prescription (PIP), and polypharmacy. Average treatment effects of access to team-based care were estimated using a difference-in-differences estimator. Results: The risk of an ADR was 22 % higher (RR = 1.22, 95 % CI = 1.18, 1.26) for older adults rostered to a team-based FP in Québec and 6 % lower (RR = 0.943, 95 % CI = 0.907, 0.978) in Ontario. However, absolute risk differences were less than 0.5 %. Differences in the risk of polypharmacy were small in Québec (RR = 1.005, 95 % CI = 1.001, 1.009) and Ontario (RR = 1.004, 95 % CI = 1.001, 1.007) and had absolute risk differences of less than 1 % in both provinces. Effects on PIP were not statistically or clinically significant in adjusted models. Interpretation: We did not find evidence that access to team-based primary care in Ontario or Québec meaningfully improved medication management outcomes for older adults.

9.
J Am Coll Cardiol ; 82(12): 1206-1222, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37704311

RESUMEN

BACKGROUND: We have followed a consistent, albeit evolving, strategy for the management of patients with pulmonary atresia or severe stenosis and major aortopulmonary collateral arteries (MAPCAs) that aims to achieve complete repair with low right ventricular pressure by completely incorporating blood supply and relieving stenoses to all lung segments. OBJECTIVES: The purpose of this study was to characterize our 20-year institutional experience managing patients with MAPCAs. METHODS: We reviewed all patients who underwent surgery for MAPCAs and biventricular heart disease from November 2001 through December 2021. RESULTS: During the study period, 780 unique patients underwent surgery. The number of new patients undergoing surgery annually was relatively steady during the first 15 years, then increased substantially thereafter. Surgery before referral had been performed in almost 40% of patients, more often in our recent experience than earlier. Complete repair was achieved in 704 patients (90%), 521 (67%) during the first surgery at our center, with a median right ventricular to aortic pressure ratio of 0.34 (25th, 75th percentiles: 0.28, 0.40). The cumulative incidence of mortality was 15% (95% CI: 12%-19%) at 10 years, with no difference according to era of surgery (P = 0.53). On multivariable Cox regression, Alagille syndrome (HR: 2.8; 95% CI: 1.4-5.7; P = 0.004), preoperative respiratory support (HR: 2.0; 95% CI: 1.2-3.3; P = 0.008), and palliative first surgery at our center (HR: 3.5; 95% CI: 2.3-5.4; P < 0.001) were associated with higher risk of death. CONCLUSIONS: In a growing pulmonary artery reconstruction program, with increasing volumes and an expanding population of patients who underwent prior surgery, outcomes of patients with pulmonary atresia or stenosis and MAPCAs have continued to improve.


Asunto(s)
Cardiopatías Congénitas , Atresia Pulmonar , Humanos , Aorta , Constricción Patológica , Arteria Pulmonar/cirugía , Atresia Pulmonar/cirugía
10.
Ann Thorac Surg ; 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37625611

RESUMEN

BACKGROUND: Various bioprosthetic valves are used off-label for pulmonary valve replacement (PVR), but there is no consensus on whether a particular valve is best for this application. Recently, the Inspiris Resilia valve (Edwards Lifesciences Inc) was approved for aortic valve replacement, and surgeons have begun using it for PVR. There is limited evidence on the performance of the Inspiris valve compared with other valves in the pulmonary position. METHODS: This study reviewed all patients who underwent PVR with a size 19- to 29-mm Inspiris valve or Mosaic valve (Medtronic Inc) from 2007 to 2022 at Lucile Packard Children's Hospital Stanford (Palo Alto, CA). Midterm outcomes included freedom from moderate or severe pulmonary regurgitation (PR), a maximum Doppler gradient ≥36 mm Hg, and freedom from reintervention. RESULTS: A total of 225 consecutive patients who underwent PVR with a size 19- to 29-mm Mosaic (n = 163) or Inspiris (n = 62) valve were included. There was no difference in baseline characteristics. Early postoperative gradients were low in both groups but higher in the Mosaic cohort, and neither group had more than mild PR on discharge. On univariable and multivariable analysis, Inspiris valves were significantly more likely to develop moderate or greater PR over time. There was no significant difference between the valves in freedom from reintervention or from a maximum gradient ≥36 mm Hg. CONCLUSIONS: Early and short-term gradients were similar in patients undergoing PVR with Inspiris and Mosaic valves, but significant PR was more common in patients who received an Inspiris valve. These preliminary findings suggest that the durability of the Inspiris valve in the pulmonary position may not be superior to that of other bioprosthetic valves used for PVR.

11.
Healthc Policy ; 18(4): 72-88, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37486814

RESUMEN

Objective: This study aims to present a proof of concept of a dashboard on a set of indicators of access to primary healthcare (PHC) based on electronic medical records (EMRs). Methods: This research builds on a multi-method design study including (1) a systematic review, (2) a pilot phase and (3) the development of a dashboard. Results: Eight indicators were carefully selected and successfully extracted from EMRs obtained from 151 PHC providers. Indicators of access over time, as well as among providers and among clinics, have been enabled in the dashboard. Conclusion: EMR data enabled the development of a real-time dashboard on access, giving PHC providers a reliable portrait of their own practice, its evolution over time and how it compares with those of their peers.


Asunto(s)
Acceso a Atención Primaria , Registros Electrónicos de Salud , Humanos , Personal de Salud , Atención Primaria de Salud
12.
Healthc Manage Forum ; 36(5): 317-321, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37326497

RESUMEN

Since 2012, implementation of the advanced access model in primary care has been highly recommended across Canada to improve timely access. We present a portrait of the implementation of the advanced access model 10 years after its large-scale implementation across the province of Quebec. In total, 127 clinics participated in the study, with 999 family physicians and 107 nurse practitioners responding to the survey. Results show that opening schedules for appointments over a period of 2 to 4 weeks has largely been implemented. However, reserving consultation time for urgent or semi-urgent conditions was implemented by less than half and planning supply and demand for 20% or more of the upcoming year by fewer than one fifth of respondents. More strategies need to be put in place to react to imbalances when they occur. We demonstrate that strategies based on individual practice change are more often implemented than those requiring changes at the clinic.


Asunto(s)
Citas y Horarios , Accesibilidad a los Servicios de Salud , Humanos , Quebec , Canadá , Encuestas y Cuestionarios
13.
BMC Prim Care ; 24(1): 97, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-37038126

RESUMEN

BACKGROUND: Improving access to primary health care is among top priorities for many countries. Advanced Access (AA) is one of the most recommended models to improve timely access to care. Over the past 15 years, the AA model has been implemented in Canada, but the implementation of AA varies substantially among providers and clinics. Continuous quality improvement (CQI) approaches can be used to promote organizational change like AA implementation. While CQI fosters the adoption of evidence-based practices, knowledge gaps remain, about the mechanisms by which QI happens and the sustainability of the results. The general aim of the study is to analyse the implementation and effects of CQI cohorts on AA for primary care clinics. Specific objectives are: 1) Analyse the process of implementing CQI cohorts to support PHC clinics in their improvement of AA. 2) Document and compare structural organisational changes and processes of care with respect to AA within study groups (intervention and control). 3) Assess the effectiveness of CQI cohorts on AA outcomes. 4) Appreciate the sustainability of the intervention for AA processes, organisational changes and outcomes. METHODS: Cluster-controlled trial allowing for a comprehensive and rigorous evaluation of the proposed intervention 48 multidisciplinary primary care clinics will be recruited to participate. 24 Clinics from the intervention regions will receive the CQI intervention for 18 months including three activities carried out iteratively until the clinic's improvement objectives are achieved: 1) reflective sessions and problem priorisation; 2) plan-do-study-act cycles; and 3) group mentoring. Clinics located in the control regions will receive an audit-feedback report on access. Complementary qualitative and quantitative data reflecting the quintuple aim will be collected over a period of 36 months. RESULTS: This research will contribute to filling the gap in the generalizability of CQI interventions and accelerate the spread of effective AA improvement strategies while strengthening local QI culture within clinics. This research will have a direct impact on patients' experiences of care. CONCLUSION: This mixed-method approach offers a unique opportunity to contribute to the scientific literature on large-scale CQI cohorts to improve AA in primary care teams and to better understand the processes of CQI. TRIAL REGISTRATION: Clinical Trials: NCT05715151.


Asunto(s)
Atención Primaria de Salud , Mejoramiento de la Calidad , Humanos , Canadá , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis por Conglomerados
14.
JTCVS Open ; 13: 344-356, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37063146

RESUMEN

Objective: Acute lung injury is a known complication of pulmonary artery reconstruction for peripheral pulmonary artery stenosis. Severe cases may require support with extracorporeal membrane oxygenation. The purpose of this study was to evaluate the characteristics of patients requiring extracorporeal membrane oxygenation after pulmonary artery reconstruction. Methods: This was a retrospective study of 150 patients who underwent surgical repair of peripheral pulmonary artery stenosis at our institution from 2002 to 2022. Underlying diagnoses included Williams syndrome (n = 44), Alagille syndrome (n = 43), elastin arteriopathy (n = 21), tetralogy of Fallot (n = 21), and other (n = 21). Characteristics of patients who required extracorporeal membrane oxygenation were compared with those who did not require extracorporeal membrane oxygenation. Results: Eleven of the 150 patients undergoing pulmonary artery reconstruction (7.3%) required postoperative extracorporeal membrane oxygenation support (10 for acute lung injury and 1 for cardiac insufficiency). Four patients receiving extracorporeal membrane oxygenation had Williams syndrome, 3 patients had Alagille, and 4 patients had tetralogy of Fallot. Patients requiring extracorporeal membrane oxygenation had a higher preoperative right ventricle to aortic peak systolic pressure ratios (mean 1.14 vs 0.95), greater number of pulmonary artery ostial interventions (median, 23 vs 17), and longer duration of cardiopulmonary bypass (median, 597 vs 400 minutes). There were 3 in-hospital deaths (2.0%), 2 of whom required postoperative extracorporeal membrane oxygenation support. Conclusions: The data demonstrate multiple differences between patients who did and did not require extracorporeal membrane oxygenation after surgical repair of peripheral pulmonary artery stenosis. These results suggest that the preoperative extent of disease may predispose to the development of acute lung injury requiring extracorporeal membrane oxygenation support.

15.
World J Pediatr Congenit Heart Surg ; 14(3): 261-272, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36972512

RESUMEN

BACKGROUND: In patients with tetralogy of Fallot and major aortopulmonary collaterals (MAPCAs), pulmonary blood supply is highly variable. Our approach to this condition emphasizes complete unifocalization of the pulmonary circulation, incorporating all lung segments and addressing stenoses out to the segmental level. Post-repair, we recommend serial lung perfusion scintigraphy (LPS) to assess short-term changes in pulmonary blood flow distribution. METHODS: We reviewed post-discharge and follow-up LPS performed through three years post-repair and analyzed serial changes in perfusion, risk factors for change, and the relationship between LPS parameters and pulmonary artery reintervention. RESULTS: Of 543 patients who had postoperative LPS results in our system, 317 (58%) had only a predischarge LPS available for review, while 226 had 1 (20%) or more (22%) follow-up scans within three years. Overall, pulmonary flow distribution prior to discharge was balanced, and there was minimal change over time; however, there was considerable patient-to-patient variation in both metrics. On multivariable mixed modeling, time after repair (P = .025), initial anatomy consisting of a ductus arteriosus to one lung (P < .001), and age at repair (P = .014) were associated with changes on serial LPS. Patients who had follow-up LPS were more likely to undergo pulmonary artery reintervention, but within that cohort, LPS parameters were not associated with reintervention risk. CONCLUSION: Serial LPS during the first year after MAPCAs repair is a noninvasive method of screening for significant post-repair pulmonary artery stenosis that occurs in a small but important minority of patients. In patients who received follow-up LPS beyond the perioperative period, there was minimal change over time in the population overall, but large changes in some patients and considerable variability. There was no statistical association between LPS findings and pulmonary artery reintervention.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Atresia Pulmonar , Tetralogía de Fallot , Humanos , Lactante , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Cuidados Posteriores , Lipopolisacáridos , Procedimientos Quirúrgicos Cardíacos/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Alta del Paciente , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Pulmón , Perfusión , Imagen de Perfusión , Circulación Colateral/fisiología , Atresia Pulmonar/cirugía
16.
Artículo en Inglés | MEDLINE | ID: mdl-36842795

RESUMEN

Williams syndrome, and various elastin protein mediated arteriopathies, presents a clinical challenge to pediatric cardiovascular specialists. In the severest phenotypes, multilevel obstruction to the systemic and pulmonic arterial systems result in biventricular dysfunction which can be imminently life-threatening. As a longstanding, quaternary referral center for complex pulmonary arteriopathies and pediatric connective tissue disease, Stanford Medicine Children's Health has developed a sizeable experience managing these patients. This manuscript is a summary of our current strategies, with a focus on our surgical techniques, peri-procedural considerations on timing and staging of various interventions, and long-term results.


Asunto(s)
Estenosis Aórtica Supravalvular , Síndrome de Williams , Humanos , Síndrome de Williams/cirugía , Estenosis Aórtica Supravalvular/cirugía , Arteria Pulmonar/cirugía , Aorta Torácica/cirugía , Corazón
17.
BMC Prim Care ; 24(1): 7, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627566

RESUMEN

BACKGROUND: Team-based primary care reforms aim to improve care coordination by involving multiple interdisciplinary health professionals in patient care. Team-based primary care may support improved medication management for older adults with polypharmacy and multiple points of contact with the healthcare system. However, little is known about this association. This study compares sociodemographic and prescribing trends among older adults in team-based vs. traditional primary care models in Ontario and Quebec. METHODS: We constructed two provincial cohorts using population-level health administrative data from 2006-2018. Our primary exposure was enrollment in a team-based model of care. Key endpoints included adverse drug events (ADEs), potentially inappropriate prescriptions (PIPs), and polypharmacy. We plotted prescribing trends across the observation period (stratified by model of care) in each province. We used standardized mean differences to compare characteristics of older adults and providers, as well as prescribing endpoints. RESULTS: Formal patient/physician enrollment increased in both provinces since the time of policy implementation; team-based enrollment among older adults was higher in Quebec (47%) than Ontario (33%) by the end of our observation period. The distribution of sociodemographic characteristics was reasonably comparable between team-based and non-team-based patients in both provinces, aside from a persistently higher share of rural patients in team-based care. Most PIPs assessed either declined or remained relatively steady over time, regardless of model of care and province. Several PIPs were more common among team-based patients than non-team-based patients, particularly in Quebec. We did not detect notable trends in ADEs or polypharmacy in either province. CONCLUSIONS: Our findings offer encouraging evidence that many PIPs are declining over time in this population, regardless of patients' enrollment in team-based care. Rates of decline appear similar across models of care, suggesting these models may not meaningfully influence prescribing endpoints. Additional efforts are needed to understand the impact of team-based care among older adults and improve primary care prescribing practices.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Prescripción Inadecuada , Humanos , Anciano , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Quebec/epidemiología , Ontario , Atención Primaria de Salud
18.
Cell Death Differ ; 30(3): 839-853, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36639541

RESUMEN

Taf4 (TATA-box binding protein-associated factor 4) is a subunit of the general transcription factor TFIID, a component of the RNA polymerase II pre-initiation complex that interacts with tissue-specific transcription factors to regulate gene expression. Properly regulated gene expression is particularly important in the intestinal epithelium that is constantly renewed from stem cells. Tissue-specific inactivation of Taf4 in murine intestinal epithelium during embryogenesis compromised gut morphogenesis and the emergence of adult-type stem cells. In adults, Taf4 loss impacted the stem cell compartment and associated Paneth cells in the stem cell niche, epithelial turnover and differentiation of mature cells, thus exacerbating the response to inflammatory challenge. Taf4 inactivation ex vivo in enteroids prevented budding formation and maintenance and caused broad chromatin remodeling and a strong reduction in the numbers of stem and progenitor cells with a concomitant increase in an undifferentiated cell population that displayed high activity of the Ezh2 and Suz12 components of Polycomb Repressive Complex 2 (PRC2). Treatment of Taf4-mutant enteroids with a specific Ezh2 inhibitor restored buddings, cell proliferation and the stem/progenitor compartment. Taf4 loss also led to increased PRC2 activity in cells of adult crypts associated with modification of the immune/inflammatory microenvironment that potentiated Apc-driven tumorigenesis. Our results reveal a novel function of Taf4 in antagonizing PRC2-mediated repression of the stem cell gene expression program to assure normal development, homeostasis, and immune-microenvironment of the intestinal epithelium.


Asunto(s)
Proteínas de Drosophila , Células Madre , Ratones , Animales , Diferenciación Celular/genética , Células Madre/metabolismo , Factor de Transcripción TFIID/genética , Mucosa Intestinal/metabolismo , Proteínas de Drosophila/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Epigénesis Genética
19.
Ann Thorac Surg ; 115(4): 981-982, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36470570
20.
J Neurotrauma ; 40(11-12): 1060-1074, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36394952

RESUMEN

Traumatic brain injury (TBI) is known to be a signature wound of the post-9/11 conflicts. In response, the U.S. Department of Defense (DOD) and other federal organizations have directed significant investments toward TBI research on characterizing injury populations and understanding long-term outcomes. To address legislative requirements and research gaps, several observational, longitudinal TBI studies were initiated as an effective means of investigating TBI clinical management, outcomes, and recovery. This review synthesizes the landscape (i.e., requirements and gaps, infrastructure, geography, timelines, TBI severity definitions, military and injury populations of interest, and measures) of DOD-funded longitudinal TBI studies being conducted in service member and veteran (SMV) populations. Based on the landscape described here, we present recommended actions and solutions that would allow a consolidated and cooperative future state of longitudinal TBI research, optimized continued investments, and advances in the state of the science without redundancy.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Personal Militar , Veteranos , Humanos , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Estudios Longitudinales
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA