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1.
Int J Equity Health ; 18(1): 200, 2019 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-31870364

RESUMEN

BACKGROUND: Poverty is associated with increased morbidity related to multiple child and adult health conditions and increased risk of premature death. Despite robust evidence linking income and health, and some recommendations for universal screening, poverty screening is not routinely conducted in clinical care. METHODS: We conducted an exploratory study of implementing universal poverty screening and intervention in family medicine and a range of pediatric care settings (primary through tertiary). After attending a training session, health care providers (HCPs) were instructed to perform universal screening using a clinical poverty tool with the question "Do you ever have difficulty making ends meet at the end of the month?" for the three-month implementation period. HCPs tracked the number of patients screened and a convenience sample of their patients were surveyed regarding the acceptability of being screened for poverty in a healthcare setting. HCPs participated in semi-structured focus groups to explore barriers to and facilitators of universal implementation of the tool. RESULTS: Twenty-two HCPs (10 pediatricians, 9 family physicians, 3 nurse practitioners) participated and 150 patients completed surveys. Eighteen HCPs participated in focus groups. Despite the self-described motivation of the HCPs, screening rates were low (9% according to self-reported numbers). The majority of patients either supported (72%) or were neutral (22%) about the appropriateness of HCPs screening for and intervening on poverty. HCPs viewed poverty as relevant to clinical care but identified time constraints, physician discomfort, lack of expertise and habitual factors as barriers to implementation of universal screening. CONCLUSIONS: Poverty screening is important and acceptable to clinicians and patients. However, multiple barriers need to be addressed to allow for successful implementation of poverty screening and intervention in health care settings.


Asunto(s)
Medicina Familiar y Comunitaria/estadística & datos numéricos , Tamizaje Masivo/organización & administración , Pediatría/estadística & datos numéricos , Pobreza , Adulto , Canadá , Niño , Humanos , Determinantes Sociales de la Salud
2.
BMC Med Educ ; 19(1): 195, 2019 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-31185964

RESUMEN

BACKGROUND: The rapid expansion of genetic knowledge, and the implications for healthcare has resulted in an increased role for Primary Care Providers (PCPs) to incorporate genetics into their daily practice. The objective of this study was to explore the self-identified needs, including educational needs, of both urban and rural Primary Care Providers (PCPs) in order to provide genetic care to their patients. METHODS: Using a qualitative grounded theory approach, ten key informant interviews, and one urban and two rural PCP focus groups (FGs) (n = 19) were conducted. All PCPs practiced in Southeastern Ontario. Data was analyzed using a constant comparative method and thematic design. The data reported here represent a subset of a larger study. RESULTS: Participants reported that PCPs have a responsibility to ensure patients receive genetic care. However, specific roles and responsibilities for that care were poorly defined. PCPs identified a need for further education and resources to enable them to provide care for individuals with genetic conditions. Based on the findings, a progressive stepped model that bridges primary and specialty genetic care was developed; the model ranged from PCPs identifying patients with genetic conditions that they could manage alone, to patients who they could manage with informal or electronic consultation to those who clearly required specialist referral. CONCLUSIONS: PCPs identified a need to integrate genetics into primary care practice but they perceived barriers including a lack of knowledge and confidence, access to timely formal and informal consultation and clearly defined roles for themselves and specialists. To address gaps in PCP confidence in providing genetic care, interventions that are directed at accessible just-in-time support and consultation have the potential to empower PCPs to manage patients' genetic conditions. Specific attention to content, timing, and accessibility of educational interventions is critical to address the needs of both urban and rural PCPs. A progressive framework for bridging primary to specialty care through a 'stepped' model for providing continuing medical education, and genetic care can was developed and can be used to guide future design and delivery of educational interventions and resources.


Asunto(s)
Genética Médica , Evaluación de Necesidades , Médicos de Atención Primaria , Adulto , Femenino , Grupos Focales , Genética Médica/educación , Teoría Fundamentada , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Ontario , Médicos de Atención Primaria/educación
3.
J Obstet Gynaecol Can ; 40(8): 1024-1030, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30103875

RESUMEN

OBJECTIVE: Short and long interpregnancy intervals (IPIs) have been associated with various adverse outcomes, and a 2016 American College of Obstetricians and Gynecologists' Committee Opinion recommends an optimal IPI of 18 months to 5 years. Descriptive data on the IPI in Canada are lacking. The objective of this study was to examine IPIs in a Manitoba cohort. METHODS: The study analyzed a subset of records from a larger dataset used to examine the IPI and adverse perinatal outcomes. For that study, Manitoba's Hospital Abstracts data were searched to identify births from 1985 to 2014. Each two consecutive live births to the same mother formed a sibling pair. The IPI was calculated as the interval between the two siblings' births, minus the younger sibling's GA. Information on maternal characteristics was extracted from various datasets housed in the Manitoba Population Research Data Repository. The current analysis examined second and higher-order births between 2010 and 2014. The proportion of suboptimal IPIs was determined and IPIs were cross-tabulated with birth year and maternal subgroups. RESULTS: More than half of pregnancies were conceived following a suboptimal interval. IPIs of less than 6 months - which have been associated with the highest risk of adverse outcomes - were more prevalent among certain subgroups. These included younger women as well as women who received inadequate prenatal care, smoked or drank alcohol during pregnancy, were low income, or did not graduate from high school. CONCLUSION: Suboptimal IPIs were common in this Manitoba cohort. Stakeholders should consider whether greater efforts to promote appropriate birth spacing are warranted.


Asunto(s)
Intervalo entre Nacimientos , Resultado del Embarazo/epidemiología , Atención Prenatal , Adulto , Estudios de Cohortes , Femenino , Humanos , Manitoba/epidemiología , Embarazo , Prevalencia , Sistema de Registros , Adulto Joven
4.
Paediatr Child Health ; 23(8): 509-514, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30842696

RESUMEN

BACKGROUND AND OBJECTIVES: Hypoglycemia monitoring is not recommended for most full-term newborns. We wished to determine the incidence, presentation and case characteristics of hypoglycemia in low-risk newborns. METHODS: With the assistance of the Canadian Paediatric Surveillance Program, we conducted a national study of severe hypoglycemia in apparently low-risk full-term newborns. Paediatricians who reported a case were sent a detailed questionnaire and the data were analyzed. RESULTS: All 93 confirmed cases were singletons, 56% were first-borns and 65% were male. An 8% rate of First Nations cases was twofold the population rate. Maternal hypertension rate was 23%, fourfold the general pregnancy rate. Maternal obesity was double the general pregnancy rate at 23%. Concerning signs or feeding issues were noted in 98% at the time of diagnosis. Median time to diagnosis was 4.1 hours. Mean blood glucose at intravenous (IV) start was 1.4 ± 0.5 hours (SD). Seventy-eight per cent had at least one of four potential stress indicators and were more likely to have early diagnosis (P=0.03). Major signs were present in 20%. Those cases presented later and had lower glucose levels (median=0.8 mmol/L versus 1.6 mmol/L, [P<0.001). Twenty-five per cent of cases had birth weight less than the 10th centile. Neurodevelopmental concern was reported in 20%. Of the 13 cases which had brain magnetic resonance imaging, 11 were abnormal. CONCLUSION: Hypoglycemia in unmonitored newborns is uncommon but is associated with significant morbidity. We provide a range of clues to help identify these newborns soon after birth. Widespread adoption of norm-based standards to identify small-for-gestational age infants is supported.

5.
J Obstet Gynaecol Can ; 39(11): 996-1007, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28757407

RESUMEN

OBJECTIVE: Congenital anomalies are a serious public health issue, and relatively few modifiable risk factors have been identified. Our objective was to investigate one such potential risk factor, the interpregnancy interval (IPI). METHODS: We conducted a secondary analysis of data housed at the Manitoba Centre for Health Policy. In-hospital live births and stillbirths of at least 20 weeks' gestation were identified, and consecutive births to the same mother were grouped into sibling pairs to calculate the IPI for the younger siblings of each pair. Logistic regression models were fit to examine the association between the IPI and any congenital anomaly, as well as CNS and chromosomal anomalies, while controlling for potentially confounding sociodemographic and clinical factors. RESULTS: Among 172 909 live births and stillbirths, the IPI was not significantly associated with congenital anomalies overall or with chromosomal anomalies. Short IPIs were associated with significantly increased odds of CNS anomalies relative to IPIs of 18-23 months (adjusted OR [aOR] for IPIs <6 months 2.15; 95% CI 1.48-3.12), whereas the aOR for IPIs ≥60 months was elevated but not statistically significant (aOR 1.50; 95% CI 0.96-2.34). In a sensitivity analysis in which the cohort was restricted to births from 2003 onwards (which yielded more complete data on health-related behaviours), the observed effect for IPIs shorter than 6 months and CNS anomalies was attenuated and no longer significant, but it remained elevated (aOR 1.65; 95% CI 0.85-3.24). CONCLUSION: The findings for CNS anomalies warrant further investigation.


Asunto(s)
Intervalo entre Nacimientos/estadística & datos numéricos , Anomalías Congénitas/epidemiología , Registros Electrónicos de Salud , Registro Médico Coordinado , Atención Prenatal/estadística & datos numéricos , Sistema de Registros , Adulto , Anomalías Congénitas/prevención & control , Femenino , Humanos , Recién Nacido , Manitoba/epidemiología , Edad Materna , Embarazo , Adulto Joven
6.
J Obstet Gynaecol Can ; 39(6): 420-433, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28363608

RESUMEN

OBJECTIVE: To examine the association between the interpregnancy interval (IPI) and preterm birth, low birth weight, and SGA birth in a developed country with universal health coverage. METHODS: We conducted a secondary analysis of data housed at the Manitoba Centre for Health Policy. All live births in Manitoba hospitals over a 29-year period were identified and consecutive births to the same mother were grouped into sibling pairs to calculate the IPI for the younger siblings. Logistic regression models were fit to examine the association between the IPI and adverse perinatal outcomes, adjusted for potentially confounding sociodemographic and clinical factors. RESULTS: In a cohort of more than 171 000 births and relative to IPIs of 18 to 23 months, IPIs shorter than 12 and longer than 23 months were associated with significantly increased odds of preterm birth overall and both medically indicated and spontaneous preterm births, low birth weight, and SGA birth. The strongest association observed was for intervals shorter than 6 months and spontaneous preterm birth (adjusted OR 1.83, 95% CI 1.65-2.03). When the outcome was modelled as GA categories, the strongest association observed was for intervals shorter than 6 months and early preterm birth (<34 weeks' GA; adjusted OR 2.47, 95% CI 2.07-2.94). CONCLUSION: If the associations observed between the IPI and adverse perinatal outcomes in this large, population-based cohort are causal, birth spacing could form an important target of public health messaging in Canada.


Asunto(s)
Intervalo entre Nacimientos/estadística & datos numéricos , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Manitoba/epidemiología , Embarazo , Adulto Joven
7.
Paediatr Child Health ; 19(7): 362-6, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25332675

RESUMEN

BACKGROUND: While written action plans are standard in the treatment and management of asthma, significant variability exists in the content and format among plans. This variability results in inconsistent educational messages that lend themselves to patient confusion and suboptimal health outcomes. OBJECTIVES: To assess the content of Canadian paediatric written action plans for consistency in format, layout, zone-defining symptoms, suggested treatment options and adherence to current Canadian asthma care guidelines. METHODS: Written action plans were sought from Canadian paediatric hospitals, major teaching hospitals associated with academic centres and three national organizations, for a total of 17 plans. An analysis was performed to assess the similarities and differences among plans. RESULTS: Of all the Canadian paediatric written action plans, 76% were found to consist of three zones and 82% incorporated a traffic light-style design. The plans were divided between symptom-based (59%) and combined symptom- and peak-flow rate approaches (41%). Nominal concordance with the 2012 Canadian Thoracic Society guidelines existed with respect to inhaled corticosteroid and oral corticosteroid therapy. Considerable variability existed among the symptom descriptors that defined each zone. Greater consistency existed among treatment strategies, although the suggested treatment was often difficult to ascertain from the plan templates. CONCLUSION: Canadian written action plans would be improved by nationally clarifying the symptom descriptors for each zone, adding asthma trigger information to the plans, increasing the emphasis of the common cold as a potential harbinger of worsening asthma symptoms and further incorporating national guideline recommendations.


HISTORIQUE: Les plans d'action écrits sont la norme pour traiter et prendre en charge l'asthme, mais leur contenu et leur présentation varient énormément. Cette variabilité s'associe à des messages d'éducation non uniformes qui favorisent la confusion des patients et des résultats de santé sous-optimaux. OBJECTIFS: Évaluer le contenu des plans d'action canadiens écrits en pédiatrie pour vérifier l'uniformité de la présentation, de la disposition, des symptômes définissant la zone, des possibilités thérapeutiques suggérées et de l'adhérence aux lignes directrices canadiennes à jour sur l'asthme. MÉTHODOLOGIE: Les chercheurs ont obtenu les plans d'action écrits des hôpitaux pédiatriques canadiens, des grands hôpitaux d'enseignement associés à des centres universitaires et de trois organisations internationales, pour un total de 17 plans. Ils ont effectué une analyse pour évaluer les similarités et les différences entre les plans. RÉSULTATS: Il a été établi que 76 % des plans d'action canadiens écrits en pédiatrie se divisaient en trois zones et que 82 % étaient structurés selon le principe des feux de signalisation. Ils étaient répartis entre une approche fondée sur les symptômes (59 %) et une approche combinant les symptômes et le débit de pointe (41 %). Ils présentaient une concordance nominale avec les lignes directrices de la Société canadienne de thoracologie de 2012 à l'égard des corticoïdes inhalés et des corticoïdes oraux. On constatait une importante variabilité quant aux descripteurs des symptômes qui définissaient chaque zone. Les stratégies thérapeutiques étaient plus uniformes, même si le traitement proposé était souvent difficile à déterminer d'après les modèles du plan. CONCLUSION: On améliorerait les plans d'action canadiens écrits si, sur la scène nationale, on clarifiait les descripteurs des symptômes dans chaque zone, on y ajoutait l'information sur les déclencheurs de l'asthme, on insistait davantage sur le rhume banal comme prédicteur potentiel d'aggravation des symptômes de l'asthme et on intégrait davantage les recommandations sur les lignes directrices nationales.

8.
Antimicrob Agents Chemother ; 56(4): 2037-47, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22290969

RESUMEN

Community-acquired pneumonia (CAP) continues to be a major health challenge in the United States and globally. Factors such as overprescribing of antibiotics and noncompliance with dosing regimens have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global phase III noninferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild to moderate CAP. Study CL05-001 demonstrated an 83.1% clinical cure rate in the cethromycin group compared with 81.1% in the clarithromycin group (95% confidence interval [CI], -4.8%, +8.9%) in the intent to treat (ITT) population and a 94.0% cethromycin clinical cure rate compared with a 93.8% clarithromycin cure rate (95% CI, -4.5%, +5.1%) in the per protocol clinical (PPc) population. Study CL06-001 achieved an 82.9% cethromycin clinical cure rate in the ITT population compared with an 88.5% clarithromycin cure rate (95% CI, -11.9%, +0.6%), whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group (95% CI, -9.1%, +0.3%). Both studies met the primary endpoints for clinical cure rate based on predefined, sliding-scale noninferiority design. Therefore, in comparison with clarithromycin, these two noninferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects with Streptococcus pneumoniae bacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.


Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Cetólidos/uso terapéutico , Neumonía/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Claritromicina/efectos adversos , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Método Doble Ciego , Determinación de Punto Final , Etnicidad , Femenino , Humanos , Cetólidos/efectos adversos , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Neumonía/microbiología , Factores Sexuales , Resultado del Tratamiento , Adulto Joven
10.
SLAS Discov ; 26(9): 1079-1090, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34269109

RESUMEN

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.


Asunto(s)
COVID-19/diagnóstico por imagen , Ensayos Analíticos de Alto Rendimiento/métodos , Citometría de Imagen/métodos , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , COVID-19/diagnóstico , COVID-19/virología , Permeabilidad de la Membrana Celular/genética , Descubrimiento de Drogas , Células Endoteliales/ultraestructura , Células Endoteliales/virología , Humanos , Procesamiento de Imagen Asistido por Computador , Pandemias/prevención & control , Fenotipo , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Arteria Pulmonar/virología , Edema Pulmonar/diagnóstico , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/virología , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/virología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/diagnóstico por imagen , Insuficiencia Respiratoria/virología , SARS-CoV-2/patogenicidad , Trombina/farmacología , Factor de Necrosis Tumoral alfa/farmacología
11.
Bioorg Med Chem Lett ; 20(18): 5389-93, 2010 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-20719505

RESUMEN

Apoptosis is a highly regulated process by which excessive cells are eliminated in order to maintain normal cell development and tissue homeostasis. Resistance to apoptosis often contributes to failure in cancer prevention and treatment. Apoptotic cell death regulators are considered important targets for discovery and development of new therapeutic agents in oncology research. A class of novel aza-lupane triterpenoids were designed, synthesized, and evaluated for antitumor activity against a panel of cancer cell lines of different histogenic origin and for ability to induce apoptosis. 3,30-Bis(aza) derivatives were identified not only to possess improved cytotoxicity compared to the natural product betulinic acid but also to affect cell death predominantly via apoptosis, whereas the mono(aza) derivatives apparently triggered cell death via different, non-apoptotic pathway(s).


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Triterpenos/química , Triterpenos/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/tratamiento farmacológico , Triterpenos Pentacíclicos , Relación Estructura-Actividad , Triterpenos/síntesis química , Ácido Betulínico
12.
Paediatr Child Health ; 20(1): 52, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25722644
13.
Early Hum Dev ; 146: 105073, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32470765

RESUMEN

OBJECTIVES: The aim of this study was to assess the efficacy of a visual noise feedback system and "quiet time" in reducing noise levels in the neonatal intensive care unit (NICU). DESIGN: A prospective cross-sectional study was performed in a combined level II/III NICU at a Canadian tertiary care hospital. Noise levels were recorded continuously for three weeks without and then three weeks with visual noise feedback system. Noise levels were compared after one year of using visual feedback, and subsequently with the addition of two "quiet times." RESULTS: Visual feedback reduced noise levels from 54.2 dB (95% CI 53.8-54.7 dB) to 49.4 dB (95% CI 48.9-49.8 dB; P < 0.0001) and increased the amount of time spent under 45 dB from 0 to 25% (P < 0.0001) after three weeks of use. However, this effect was not sustained at one year of visual feedback, with noise levels at 54.7 dB (95% CI 54.5-55.0 dB, P = 0.55). Quiet Time did not further reduce daily noise in the NICU (average noise levels 54.7, 95% CI 54.4-55.0 dB, P = 0.836). CONCLUSIONS: While visual noise feedback system reduced noise levels in the short term, these effects were not sustainable at one year and could not be remediated with the addition of a Quiet Time initiative. Continuing education regarding the detrimental effects of noise is paramount to ensure persistent noise reduction in the NICU.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal/organización & administración , Ruido/prevención & control , Estudios Transversales , Retroalimentación , Humanos , Ontario , Estudios Prospectivos , Centros de Atención Terciaria
14.
Bioorg Med Chem Lett ; 19(8): 2168-71, 2009 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-19286375

RESUMEN

New A-ring modified betulin and dihydrobetulin derivatives possessing the 2-cyano-1-en-3-one moiety were prepared and tested for cytotoxicity in seven cancer cell lines. The most active agent 9a synthesized in this account was further demonstrated to induce apoptosis and to activate caspases in malignant melanoma cells.


Asunto(s)
Inhibidores de Crecimiento/síntesis química , Inhibidores de Crecimiento/toxicidad , Triterpenos/síntesis química , Triterpenos/toxicidad , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Triterpenos Pentacíclicos , Ácido Betulínico
15.
J Obstet Gynaecol Can ; 31(6): 497-503, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19646314

RESUMEN

OBJECTIVE: The primary objective of this study was to determine the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI) to assess white matter changes in high-risk neonates. Secondary objectives were to determine if exposure to chorioamnionitis (clinical or histopathologic) is associated with DWMRI findings in the neonatal brain, and to calculate the sample size required for a more definitive prospective cohort study. METHODS: Seventeen women with PPROM (preterm premature rupture of the membranes) who delivered 18 infants not requiring ventilatory support were recruited to participate in this case series. When stable, infants underwent DWMRI scanning. All placentas were examined for evidence of histopathologic chorioamnionitis (HCA). RESULTS: There was histopathologic evidence of chorioamnionitis in seven of the 18 placentas examined; three of these patients had clinical chorioamnionitis. Diffusion MRI revealed changes in both the diffusion-weighted imaging and the apparent diffusion coefficient in three of the seven infants confirmed to have HCA (43%), while only one of the 11 infants with normal placentas (9%) showed similar findings. Routine head ultrasound examination demonstrated abnormal cortical findings that would normally prompt further investigation in only one of these infants. CONCLUSION: Exposure to HCA may be associated with abnormal DWMRI findings on imaging of the neonatal brain within 96 hours of delivery. Further study is required to delineate the association of chorioamnionitis and white matter changes with long-term neurodevelopmental sequelae.


Asunto(s)
Encéfalo/patología , Corioamnionitis/patología , Imagen de Difusión por Resonancia Magnética , Adulto , Estudios de Factibilidad , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Factores de Tiempo
16.
J Epidemiol Community Health ; 73(10): 920-928, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31358534

RESUMEN

BACKGROUND: A high maternal prepregnancy body mass index has been associated with lower offspring IQ, but it is unclear if the relationship is causal. To explore this, our objectives were to compare maternal and paternal estimates and to assess whether certain factors mediate the association. METHODS: We analysed data from the Avon Longitudinal Study of Parents and Children, which initially recruited 14 541 women residing in Avon, UK, with an expected date of delivery in 1991-1992. Data were collected during and after pregnancy by questionnaire, medical record abstraction and clinical assessment. At approximately 8 years of age, psychologists administered an abbreviated form of the Wechsler Intelligence Scale for Children-III. We fit multivariable logistic regression models to estimate parental prepregnancy obesity and overweight-offspring IQ associations. Counterfactually defined indirect (mediated) effects of maternal prepregnancy obesity on offspring IQ were estimated through path analysis. RESULTS: Among 4324 mother-father-child triads and using normal weight as the referent, we observed consistently stronger associations for maternal prepregnancy obesity and offspring performance IQ (eg, adjusted ß (95% CI)=-3.4 (-5.7 to -1.2) vs -0.97 (-2.9 to 0.96) for paternal obesity). The indirect effects of maternal obesity on offspring IQ through pathways involving gestational weight gain and duration of breastfeeding were small but significant. CONCLUSION: Our findings are consistent with a weak biologic effect of maternal adiposity in pregnancy on offspring performance IQ. Given the growing prevalence of obesity worldwide, more evidence is needed to resolve the correlation versus causation debate in this area.


Asunto(s)
Índice de Masa Corporal , Pruebas de Inteligencia , Adulto , Niño , Inglaterra , Femenino , Humanos , Estudios Longitudinales , Masculino , Modelos Teóricos , Embarazo , Prevalencia , Encuestas y Cuestionarios
17.
BMC Mol Cell Biol ; 20(1): 10, 2019 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-31109284

RESUMEN

BACKGROUND: Focal Adhesion Kinase (FAK) is a major cancer drug target that is involved in numerous aspects of tumor progression and survival. While multiple research groups have developed ATP-competitive small molecule inhibitors that target the kinase enzyme, recent attention has been focused on the FAK FERM (Band 4.1, Ezrin, Radixin, Moesin) domain that contains key residue Y397 and contributes to many protein-protein interactions. Previous x-ray crystal structures of the FAK FERM domain gave conflicting results on the structure of the Y397 region and therefore the overall druggability. RESULTS: Here, we report the identification of a higher resolution crystal structure of the avian FAK FERM domain that shows conformational differences in Y397 and surrounding residues in the F1 lobe. In addition, we resolve the residues of the Src SH3 binding site, an area of the FERM domain that has previously shown limited electron density. CONCLUSIONS: These crystallographic data suggest that the Y397 region is highly dynamic and question the druggability of a putative pocket on the F1 lobe. In addition, new electron density data around the Src SH3 binding site provide structural insight on the FAK-Src activation cascade through a putative auto-inhibitory conformation.


Asunto(s)
Proteínas Aviares/química , Cristalización , Dominios FERM , Proteína-Tirosina Quinasas de Adhesión Focal/química , Proteínas Proto-Oncogénicas pp60(c-src)/química , Tirosina/química , Dominios Homologos src , Animales , Sitios de Unión , Simulación por Computador , Cristalografía por Rayos X , Proteínas del Citoesqueleto/química , Dimerización , Descubrimiento de Drogas/métodos , Proteína-Tirosina Quinasas de Adhesión Focal/antagonistas & inhibidores , Proteínas de la Membrana/química , Proteínas de Microfilamentos/química , Fosforilación , Unión Proteica , Estructura Secundaria de Proteína
18.
J Community Genet ; 10(1): 85-93, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29700759

RESUMEN

To effectively translate genetic advances into practice, engagement of primary care providers (PCPs) is essential. Using a qualitative, phenomenological methodology, we analyzed key informant interviews and focus groups designed to explore perspectives of urban and rural PCPs. PCPs endorsed a responsibility to integrate genetics into their practices and expected advances in genetic medicine to expand. However, PCPs reported limited knowledge and difficulties accessing resources, experts, and continuing education. Rural practitioners' additional concerns included cost, distance, and poor patient engagement. PCPs' perspectives are crucial to develop relevant educational and systems-based interventions to further expand genetic medicine in primary care.

19.
Neurosci Lett ; 445(3): 233-5, 2008 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-18801411

RESUMEN

Chorioamnionitis, a perinatal infection of the fetal membranes, and maternal fever, which often accompanies infection are both risk factors for cerebral palsy (CP). Inflammation is a typical reaction to infection. Thus the aim of this study was to determine if hyperthermia alters newborn rat brain inflammatory response and oxidant stress after a maternal rat lipopolysaccaharide (LPS) injection. Since chorioamnionitis can predispose the fetus to perinatal hypoxia, we also explored the interaction with postnatal hypoxia. Exposure of newborn pups to brief hypoxia alone significantly increased brain tumor necrosis factor-alpha (TNF-alpha) and slightly increased levels of nitrite/nitrate. When maternal LPS was combined with postnatal hypoxia, the levels of TNF-alpha in were further increased when compared with hypoxia alone. Exposure of newborn pups to hyperthermia at 39 degrees C following maternal LPS and hypoxia caused yet more significant increases in brain TNF-alpha, nitrite/nitrate, and MDA/4-HAD compared to that under normal temperature conditions. This study supports the hypothesis that fever is a significant modifier of brain inflammatory response in developing brain particularly in a setting of hypoxia.


Asunto(s)
Encéfalo/metabolismo , Citocinas/metabolismo , Hipertermia Inducida/métodos , Inflamación/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Encéfalo/inmunología , Modelos Animales de Enfermedad , Femenino , Hipoxia/patología , Inflamación/inducido químicamente , Peroxidación de Lípido/efectos de los fármacos , Lipopolisacáridos , Nitratos/metabolismo , Nitritos/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
20.
Braz J Anesthesiol ; 68(3): 318-321, 2018.
Artículo en Portugués | MEDLINE | ID: mdl-29657064

RESUMEN

BACKGROUND: Selective neonatal left mainstem bronchial intubation to treat right lung disease is typically achieved with elaborate maneuvers, instrumentation and devices. This is often attributed to bronchial geometry which favors right mainstem entry of an endotracheal tube deliberately advanced beyond the carina. CASE SUMMARY: A neonate with severe bullous emphysema affecting the right lung required urgent non-ventilation of that lung. We achieved left mainstem bronchial intubation by turning the endotracheal tube 180° such that the Murphy's eye faced the left instead of the right, and simulated a left-handed intubation by slightly orientating the endotracheal tube such that its concavity faced the left instead of the right as in a conventional right-handed intubation. CONCLUSION: Urgent intubation of the left mainstem bronchus with an endotracheal tube can be easily achieved by recognizing that it is the position of the endotracheal tube tip and the direction of its concavity that are the chief determinants of which bronchus an endotracheal tube goes when advanced. This is important in critically ill neonates as the margin of safety and time window are small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and blockers should be reserved as backup plans.

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