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1.
Pediatr Transplant ; 28(1): e14584, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37470130

RESUMO

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.


Assuntos
Transplante de Coração , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Criança , Doadores de Tecidos , Coração , Fatores de Risco
2.
Qual Health Res ; : 10497323241237411, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501324

RESUMO

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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36842795

RESUMO

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.


Assuntos
Estenose Aórtica Supravalvular , Síndrome de Williams , Humanos , Síndrome de Williams/cirurgia , Estenose Aórtica Supravalvular/cirurgia , Artéria Pulmonar/cirurgia , Aorta Torácica/cirurgia , Coração
4.
Healthc Manage Forum ; 36(5): 317-321, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37326497

RESUMO

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.


Assuntos
Agendamento de Consultas , Acessibilidade aos Serviços de Saúde , Humanos , Quebeque , Canadá , Inquéritos e Questionários
5.
Pediatr Crit Care Med ; 23(5): 371-377, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213412

RESUMO

OBJECTIVES: We have previously shown that patients with a chromosome 22q11 microdeletion are at risk for prolonged respiratory failure after pulmonary artery reconstruction surgery compared with those with normal genotype. We sought to describe preexisting airway abnormalities in this patient population and examine relationships between airway abnormalities and outcomes. DESIGN: Single-center retrospective chart review from Society of Thoracic Surgery and Pediatric Cardiac Critical Care Consortium databases and the electronic medical record. SETTING: Lucile Packard Children's Hospital at Stanford from September 2017 to February 2019. PATIENTS: All patients undergoing pulmonary artery reconstruction surgery were considered for inclusion. INTERVENTIONS: We identified 127 patients meeting study inclusion criteria. Thirty-nine patients met specific criteria and underwent screening preoperative bronchoscopy including microdirect laryngoscopy and lower airway examination. Postoperative bronchoscopy was performed at the discretion of the intensive care team. MEASUREMENTS AND MAIN RESULTS: Airway abnormalities were detected in 25/26 of children (96%) with a chromosome 22q11 deletion who underwent preoperative bronchoscopy. Upper and lower airway pathologies were found in 19/25 (73%) and 21/25 (81%) patients, respectively, and it was common for patients to have more than one abnormality. Presence of 22q11 deletion was associated with longer duration of mechanical ventilation (9.1 vs 4.3 d; p = 0.001), use of noninvasive positive pressure support (13 vs 6 d; p = 0.001), and longer hospital stays (30 vs 14 d; p = 0.002). These outcomes were worse when compared with patients with known airway abnormalities who did not have 22q11 deletion. CONCLUSIONS: Preexisting upper and lower airway pathologies are common in patients with a chromosome 22q11 deletion who undergo pulmonary artery reconstruction surgery. Despite similar postoperative hemodynamics and outcomes as their counterparts without 22q11 deletion, 22q11 deletion is associated with more postoperative respiratory complications not entirely explained by preexisting airway abnormalities.


Assuntos
Artéria Pulmonar , Insuficiência Respiratória , Broncoscopia , Criança , Deleção Cromossômica , Humanos , Pulmão , Complicações Pós-Operatórias/epidemiologia , Artéria Pulmonar/cirurgia , Insuficiência Respiratória/genética , Estudos Retrospectivos
6.
J Card Surg ; 37(10): 3028-3035, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35917407

RESUMO

BACKGROUND: Outcomes for congenital heart disease have dramatically improved over the past several decades. However, there are patients who encounter intraoperative or postoperative complications and ultimately do not survive. It was our hypothesis that the number of postoperative procedures (including surgical and unplanned diagnostic procedures) would correlate with hospital length of stay and operative mortality. METHODS: This was a retrospective review of 938 consecutive patients undergoing congenital heart surgery at a single institution over a 2-year timeframe. The number of postoperative surgical and unplanned diagnostic procedures were counted and the impact on hospital length of stay and mortality was assessed. RESULTS: 581 of the 938 (62%) patients had zero postoperative diagnostic or surgical procedures. These patients had a median length of stay of 6 days with a single operative mortality (0.2%). 357 of the 938 (38%) patients had one or more postoperative diagnostic or surgical procedures. These patients had a total of 1586 postoperative procedures. There was a significant correlation between the number of postoperative procedures and both hospital length of stay and mortality (p < .001). Patients who required 10 or more postoperative procedures had a median hospital length of stay of 89 days and had a 50% mortality. There were no survivors in patients who had 15 or more postoperative procedures. CONCLUSIONS: The data demonstrate that the number of postoperative procedures was highly correlated with both hospital length of stay and mortality.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Mortalidade Hospitalar , Hospitais , Humanos , Tempo de Internação , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco
7.
Hemoglobin ; 45(1): 62-65, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33622170

RESUMO

Transition of adolescents with sickle cell disease to adult programs is associated with increased morbidity and mortality. The reasons for this poor outcome are not well known. This report describes the various factors that affect the outcome of the transition process. These include four inter-personal factors: country of residence, region within the country of residence, the health care system and intra-personal factors. Each factor is described in some detail. Understanding these factors and the establishment of guidelines or recommendations could improve the outcome of this critical transition in the life of patients with sickle cell disease.


Assuntos
Anemia Falciforme , Adolescente , Anemia Falciforme/terapia , Humanos
8.
Int J Equity Health ; 19(1): 94, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522215

RESUMO

BACKGROUND: There are shortcomings in medical practitioners' capacity to adapt to the particular needs of people experiencing circumstances of social vulnerability. Clinical traineeships create opportunities for the acquisition of knowledge, competencies, attitudes, and behaviors. However, some authors question the learnings to be made through classical clinical training pathways. This article explores the learnings gained from a traineeship experience within a community-based clinical setting intended for patients experiencing social vulnerability and operating under an alternative paradigm of care. To our knowledge, there is little research intended to identify and understand what medical trainees gain from their experience in such contexts. METHODS: This exploratory qualitative study is based on twelve interviews with practicing physicians who completed a traineeship at La Maison Bleue (Montreal, Canada) and three interviews conducted with key informants involved in traineeship management. Based on Mezirow's theory of transformational learning, data were analyzed according to L'Écuyer's principles of qualitative content analysis. NVivo software was used. RESULTS: The main learnings gained through the traineeship are related to (1) greater awareness of beliefs, assumptions and biases through prejudice deconstruction, cultural humility and critical reflection on own limitations, power and privileges; (2) the development of critical perspectives regarding the health care system; (3) a renewed vision of medical practice involving a less stigmatizing approach, advocacy, empowerment, interdisciplinarity and intersectorality; and (4) strengthened professional identity and future practice orientation including confirmation of interest for community-based practice, the identification of criteria for choosing a future practice setting, and commitment to becoming an actor of social change. Certain characteristics of the setting, the patients and the learner's individual profile are shown to be factors that promote these learnings. CONCLUSIONS: This article highlights how a traineeship experience within a clinical setting intended for a clientele experiencing circumstances of social vulnerability and operating under an alternative paradigm presents an opportunity for transformative learning and health practice transformation toward renewed values of health equity and social justice. Our findings suggest medical traineeships in community-based clinical settings are a promising lead to foster the development of fundamental learnings that are conducive to acceptable and equitable care for people experiencing social vulnerability.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Currículo , Educação Médica/organização & administração , Equidade em Saúde , Disparidades em Assistência à Saúde , Médicos/psicologia , Apoio ao Desenvolvimento de Recursos Humanos/organização & administração , Adulto , Canadá , Feminino , Humanos , Masculino , Pesquisa Qualitativa
9.
Semin Cell Dev Biol ; 62: 178-186, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27422329

RESUMO

SERPINB1, also called Leukocyte Elastase Inhibitor (LEI) is a member of the clade B of SERPINS. It is an intracellular protein and acts primarily to protect the cell from proteases released into the cytoplasm during stress. Its role in inflammation is clear due to its involvement in the resolution of chronic inflammatory lung and bowel diseases. LEI/SERPINB1 intrinsically possesses two enzymatic activities: an antiprotease activity dependent on its reactive site loop, which is analogous to the other proteins of the family and an endonuclease activity which is unveiled by the cleavage of the reactive site loop. The conformational change induced by this cleavage also unveils a bipartite nuclear localization signal allowing the protein to translocate to the nucleus. Recent data indicate that it has also a role in cell migration suggesting that it could be involved in diverse processes like wound healing and malignant metastases.


Assuntos
Elastase de Leucócito/metabolismo , Inibidores de Proteases/metabolismo , Serpinas/metabolismo , Animais , Apoptose , Evolução Molecular , Humanos , Filogenia
10.
J Head Trauma Rehabil ; 33(2): 123-132, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29517592

RESUMO

OBJECTIVE: To examine mortality among active duty US military service members (SMs) with the diagnosis of penetrating traumatic brain injury (PTBI) and a hospital admission between 2004 and 2014. DESIGN: Data on SMs with PTBI and an admission to a military or civilian hospital were obtained from the 2004 to 2014 Military Health System data repository. After applying exclusion criteria, data on 1226 SMs were analyzed. MAIN MEASURES: The number of observed deaths per 100 identified patients with PTBI and time to death from admission were used as main measures. RESULTS: Approximately 25% of the 1226 patients with PTBI included in this study died following admission, with 44.6% of the all deaths occurring within a day following hospital admission and 75% occurring within the first week. Severe comorbid conditions and intentionally self-inflicted injuries are associated with higher mortality rate. SMs' gender, age, year of hospital admission, and service were significantly associated with likelihood of death following PTBI hospitalization. Males had a higher likelihood of dying following hospital admission compared with females (odds ratio = 2.7, confidence interval = 1.03-7.9). SMs in the 35- to 44-year-old and 45- to 64-year-old groups had up to a 2.6 times higher odds of death following their admission compared with the 25- to 34-year-old group. Age, admission year, service, and rank were significantly associated with SMs' time to death from hospitalization. Patients between the ages of 45 and 64 years were significantly more likely to die earlier than other age groups. Furthermore, cases in the Navy Afloat group had a higher fatality rate and were more likely to die earlier than patients in other services. PTBI comorbid conditions and injury type did not significantly affect time to death. CONCLUSION: This study quantifies case fatality rate among hospitalized US SMs with the diagnosis of PTBI. We report a 23.1% crude case fatality rate among the current cohort. Early intensive care for these patients may be the key to improving survival rates.


Assuntos
Lesões Encefálicas Traumáticas/mortalidade , Traumatismos Cranianos Penetrantes/mortalidade , Hospitalização , Militares , Adolescente , Adulto , Lesões Encefálicas Traumáticas/diagnóstico , Estudos de Coortes , Feminino , Traumatismos Cranianos Penetrantes/diagnóstico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
11.
J Clin Pharm Ther ; 43(6): 877-887, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30019341

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The literature has reported suboptimal real-world use of oral anticoagulants in patients with atrial fibrillation (AF). Anticoagulation management services (AMSs) in community pharmacy have rarely been evaluated, and no formal process is available to enable pharmacists to evaluate and improve their clinical practices. Our objective was to assess the feasibility of implementing, through a practice-based research network (PBRN), a quality improvement programme on AMSs by community pharmacists for AF patients and explore its impact on the quality of clinical practices and pharmacists' knowledge. METHODS: An uncontrolled pre/post-pilot study was conducted through a PBRN. Pharmacists identified 5-20 AF patients on oral anticoagulants per pharmacy and completed questionnaires at baseline (T0) and after 6 months (T6). Clinical practices were evaluated using a set of quality indicators (QIs). QI scores ranged from 0% (no QI achieved) to 100% (all QIs achieved). The programme included an audit and feedback based on QIs and a personalized training programme (including online videos). Participation rates and satisfaction were documented. Mean changes (T6-T0), with 95% confidence interval (CI), in QIs and knowledge scores were computed. RESULTS AND DISCUSSION: A total of 37 pharmacies (50 pharmacists) identified 222 patients who had received either vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), or both. All pharmacies received their baseline quality report (audit), and facilitators contacted by phone 97% of pharmacies (feedback). Each of the six online videos was completed by at least 48% of pharmacists. Baseline mean global QI scores for VKAs and DOACs were 39.1% (95% CI: 35.7%-42.4%) and 12.3% (7.8%-16.8%), respectively. Over a 6-month period, they increased by 12.5% points (7.5%-17.5%) and 9.9% points (3.8%-16.1%), respectively. Baseline mean global knowledge score was 68.7% (65.4%-72.0%) and increased by 4.3% points (1.2%-7.4%). WHAT IS NEW AND CONCLUSION: Implementing a quality improvement programme for AMS in community pharmacy is relevant and feasible and may improve pharmacists' practices and knowledge.


Assuntos
Anticoagulantes/administração & dosagem , Serviços Comunitários de Farmácia/organização & administração , Farmacêuticos/organização & administração , Melhoria de Qualidade , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Serviços Comunitários de Farmácia/normas , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Farmacêuticos/normas , Projetos Piloto , Papel Profissional , Indicadores de Qualidade em Assistência à Saúde
12.
Chem Eng J ; 352: 612-624, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32831624

RESUMO

Phosphorus is an essential and limited nutrient that is supplied by a depleting resource, mineral phosphate rock. Eutrophication is occurring in many water bodies which provides an opportunity to recover this nutrient from the water. One method of recovery is through adsorption; this study focused on fabricating a porous and granular adsorptive material for the removal and recovery of phosphate. Magnesium carbonate was combined with cellulose in varying weight ratios (0, 5, 10, 15, 20%) to synthesize pellets, which were then calcined to increase internal surface area. Physiochemical properties such as surface area, surface morphology, elemental composition, and crystal structure of the materials were characterized using Brunauer, Emmett, and Teller (BET) surface area analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The pellet proved to be uniform in composition and an increase in BET surface area correlated with an increase in cellulose content until pellet stability was lost. Phosphate adsorption using the pellets was studied via batch kinetics and sorption isotherms. The pseudo-second-order kinetics model fits best suggesting that the adsorption occurring was chemisorption. The isotherm model that fit best was the Langmuir isotherm, which showed that the maximum equilibrium adsorption capacity increased with an increase in cellulose content between 10% and 20%. The average adsorption capacity achieved in the triplicate isotherm study was 96.4 mg g-1 for pellets synthesized with 15% cellulose. Overall, using cellulose and subsequent calcination created an additional internal surface area for adsorption of phosphate and suggested that granular materials can be modified for efficient removal and recovery of phosphate from water.

13.
Am J Kidney Dis ; 70(3): 386-396, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28663062

RESUMO

BACKGROUND: Appropriate training for community pharmacists may improve the quality of medication use. Few studies have reported the impact of such programs on medication management for patients with chronic kidney disease (CKD). STUDY DESIGN: Multicenter, cluster-randomized, controlled trial. SETTING & PARTICIPANTS: Patients with CKD stage 3a, 3b, or 4 from 6 CKD clinics (Quebec, Canada) and their community pharmacies. INTERVENTION: Each cluster (a pharmacy and its patients) was randomly assigned to either ProFiL, a training-and-communication network program, or the control group. ProFiL pharmacists completed a 90-minute interactive web-based training program on use of medications in CKD and received a clinical guide, patients' clinical summaries, and facilitated access to the CKD clinic. OUTCOMES: Drug-related problems (primary outcome), pharmacists' knowledge and clinical skills, and patients' clinical attributes (eg, blood pressure and glycated hemoglobin concentration). MEASUREMENTS: Drug-related problems were evaluated the year before and after the recruitment of patients using a validated set of significant drug-related problems, the Pharmacotherapy Assessment in Chronic Renal Disease (PAIR) criteria. Pharmacists' questionnaires were completed at baseline and after 1 year. Clinical attributes were documented at baseline and after 1 year using available information in medical charts. RESULTS: 207 community pharmacies, 494 pharmacists, and 442 patients with CKD participated. After 1 year, the mean number of drug-related problems per patient decreased from 2.16 to 1.60 and from 1.70 to 1.62 in the ProFiL and control groups, respectively. The difference in reduction of drug-related problems per patient between the ProFiL and control groups was -0.32 (95% CI, -0.63 to -0.01). Improvements in knowledge (difference, 4.5%; 95% CI, 1.6%-7.4%) and clinical competencies (difference, 7.4%; 95% CI, 3.5%-11.3%) were observed among ProFiL pharmacists. No significant differences in clinical attributes were observed across the groups. LIMITATIONS: High proportion of missing data on knowledge and clinical skills questionnaire (34.6%) and clinical attributes (11.1%). CONCLUSIONS: Providing community pharmacists with essential clinical data, appropriate training, and support from hospital pharmacists with expertise in nephrology increases pharmacists' knowledge and reduces drug-related problems in patients with CKD who are followed up in clinics incorporating a multidisciplinary health care team.


Assuntos
Serviços Comunitários de Farmácia , Conduta do Tratamento Medicamentoso , Nefrologia/educação , Farmacêuticos/normas , Insuficiência Renal Crônica/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Competência Clínica/normas , Serviços Comunitários de Farmácia/organização & administração , Serviços Comunitários de Farmácia/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Educação/métodos , Feminino , Hemoglobinas Glicadas/análise , Acessibilidade aos Serviços de Saúde/normas , Humanos , Masculino , Conduta do Tratamento Medicamentoso/educação , Conduta do Tratamento Medicamentoso/normas , Pessoa de Meia-Idade , Gravidade do Paciente , Melhoria de Qualidade , Desenvolvimento de Pessoal/métodos , Inquéritos e Questionários
14.
Int J Qual Health Care ; 29(8): 999-1005, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29190350

RESUMO

OBJECTIVE: To assess a selection of psychometric properties of the TRANSIT indicators. DESIGN: Using medical records, indicators were documented retrospectively during the 14 months preceding the end of the TRANSIT study. SETTING: Primary care in Quebec, Canada. PARTICIPANTS: Indicators were documented in a random subsample (n = 123 patients) of the TRANSIT study population (n = 759). INTERVENTIONS: For every patient, the mean compliance to all indicators of a category (subscale score) and to the complete set of indicators (overall scale score) were established. To evaluate test-retest and inter-rater reliabilities, indicators were applied twice, two months apart, by the same evaluator and independently by different evaluators, respectively. To evaluate convergent validity, correlations between TRANSIT indicators, Burge et al. indicators and Institut national d'excellence en santé et en services sociaux (INESSS) indicators were examined. MAIN OUTCOME MEASURES: Test-retest reliability, inter-rater reliability, and convergent validity. RESULTS: Test-retest reliability, as measured by intraclass correlation coefficients (ICCs) was equal to 0.99 (0.99-0.99) for the overall scale score while inter-rater reliability was equal to 0.95 (0.93-0.97) for the overall scale score. Convergent validity, as measured by Pearson's correlation coefficients, was equal to 0.77 (P < 0.001) for the overall scale score when the TRANSIT indicators were compared to Burge et al. indicators and to 0.82 (P < 0.001) for the overall scale score when the TRANSIT indicators were compared to INESSS indicators. CONCLUSIONS: Reliability was excellent except for eleven indicators while convergent validity was strong except for domains related to the management of CVD risk factors.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Psicometria/métodos , Indicadores de Qualidade em Assistência à Saúde , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Atenção Primária à Saúde/métodos , Quebeque , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco
16.
Inorg Chem ; 54(16): 8111-20, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26251218

RESUMO

Controlling the relative and absolute configuration of octahedral metal complexes constitutes a key challenge that needs to be overcome in order to fully exploit the structural properties of octahedral metal complexes for applications in the fields of catalysis, materials sciences, and life sciences. Herein, we describe the application of a proline-based chiral tridentate ligand to decisively control the coordination mode of an octahedral rhodium(III) complex. We demonstrate the mirror-like relationship of synthesized enantiomers and differences between diastereomers. Further, we demonstrate, using the established pyridocarbazole pharmacophore ligand as part of the organometallic complexes, the importance of the relative and absolute stereochemistry at the metal toward chiral environments like protein kinases. Protein kinase profiling and inhibition data confirm that the proline-based enantiopure rhodium(III) complexes, despite having all of the same constitution, differ strongly in their selectivity properties despite their unmistakably mutual origin. Moreover, two exemplary compounds have been shown to induce different toxic effects in an ex vivo rat liver model.


Assuntos
Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Ródio/química , Animais , Humanos , Fígado/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/toxicidade , Inibidores de Proteínas Quinases/toxicidade , Ratos , Estereoisomerismo
17.
BMC Neurosci ; 15: 73, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24915960

RESUMO

BACKGROUND: Recent evidence has suggested that Alzheimer's disease (AD)-associated neuronal loss may occur via the caspase-independent route of programmed cell death (PCD) in addition to caspase-dependent mechanisms. However, the brain region specificity of caspase-independent PCD in AD-associated neurodegeneration is unknown. We therefore used the transgenic CRND8 (TgCRND8) AD mouse model to explore whether the apoptosis inducing factor (AIF), a key mediator of caspase-independent PCD, contributes to cell loss in selected brain regions in the course of aging. RESULTS: Increased expression of truncated AIF (tAIF), which is directly responsible for cell death induction, was observed at both 4- and 6-months of age in the cortex. Concomitant with the up-regulation of tAIF was an increase in the nuclear translocation of this protein. Heightened tAIF expression or translocation was not observed in the hippocampus or cerebellum, which were used as AD-vulnerable and relatively AD-spared regions, respectively. The cortical alterations in tAIF levels were accompanied by increased Bax expression and mitochondrial translocation. This effect was preceded by a significant reduction in ATP content and an increase in reactive oxygen species (ROS) production, detectable at 2 months of age despite negligible amounts of amyloid-beta peptides (Aß). CONCLUSIONS: Taken together, these data suggest that AIF is likely to play a region-specific role in AD-related caspase-independent PCD, which is consistent with aging-associated mitochondrial impairment and oxidative stress.


Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Fator de Indução de Apoptose/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Envelhecimento/patologia , Animais , Apoptose , Humanos , Camundongos , Camundongos Transgênicos , Distribuição Tecidual
18.
Nucleic Acids Res ; 40(8): 3456-69, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22189105

RESUMO

Cdx2, a gene of the paraHox cluster, encodes a homeodomain transcription factor that plays numerous roles in embryonic development and in homeostasis of the adult intestine. Whereas Cdx2 exerts a tumor suppressor function in the gut, its abnormal ectopic expression in acute leukemia is associated to a pro-oncogenic function. To try to understand this duality, we have hypothesized that Cdx2 may interact with different protein partners in the two tissues and set up experiments to identify them by tandem affinity purification. We show here that Cdx2 interacts with the Ku heterodimer specifically in intestinal cells, but not in leukemia cells, via its homeodomain. Ku proteins do not affect Cdx2 transcriptional activity. However, Cdx2 inhibits in vivo and in vitro the DNA repair activity mediated by Ku proteins in intestinal cells. Whereas Cdx2 does not affect the recruitment of Ku proteins and DNA-PKcs into the DNA repair complex, it inhibits DNA-PKcs activity. Thus, we report here a new function of Cdx2, acting as an inhibitor of the DNA repair machinery, that may contribute to its tumor suppressor function specifically in the gut.


Assuntos
Neoplasias do Colo/genética , Reparo do DNA por Junção de Extremidades , Proteínas de Homeodomínio/metabolismo , Leucemia/genética , Proteínas Supressoras de Tumor/metabolismo , Antígenos Nucleares/metabolismo , Fator de Transcrição CDX2 , Linhagem Celular Tumoral , Sobrevivência Celular , Neoplasias do Colo/metabolismo , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Etoposídeo/toxicidade , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/fisiologia , Humanos , Autoantígeno Ku , Leucemia/metabolismo , Domínios e Motivos de Interação entre Proteínas , Transcrição Gênica , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/fisiologia
19.
JACC Case Rep ; 29(8): 102304, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38774800

RESUMO

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.

20.
BMC Prim Care ; 25(1): 160, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730345

RESUMO

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.


Assuntos
Acessibilidade aos Serviços de Saúde , Internato e Residência , Quebeque , Internato e Residência/organização & administração , Estudos Transversais , Humanos , Acessibilidade aos Serviços de Saúde/organização & administração , Medicina de Família e Comunidade/educação , Atenção Primária à Saúde/organização & administração , Inquéritos e Questionários
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