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1.
Aust Crit Care ; 37(5): 747-754, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38485556

RESUMO

BACKGROUND: Umbilical catheters are commonly inserted in newborns in the neonatal intensive care unit (NICU) yet are associated with serious adverse events (AEs) such as malposition, migration, infection, thrombosis, hepatic complications, cardiac effusion, and cardiac tamponade. There is a need to determine the incidence and risk factors for AEs to inform safe practice. OBJECTIVES: The objective of this study was to determine the incidence and risk factors for AEs (all-cause and individual types) associated with umbilical venous catheters (UVCs) and umbilical arterial catheters (UACs) in the NICU. METHODS: A retrospective cohort study was conducted in an Australian level-VI NICU over a 3-year period. Any newborn who had both a UVC and UAC insertion attempt was included. RESULTS: There were 236 neonates who had 494 catheters (245 UVCs and 249 UACs). Of these, 71% of UVCs (95% confidence interval [CI]: 65.6-76.9%; incidence rate: 181.1-237.3 per 1000 catheter days) and 43.8% of UACs (95% CI: 38-50.5%; incidence rate: 102.0-146.3 per 1000 catheter days) were associated with an AE. The most common AE was malposition on first X-ray for UVCs (60.1%, 95% CI: 55.1-67.3) and UACs (32.6%, 95% CI: 26.8-39.6). A dwell time of ≥7 days was a significant predictor of UAC failure (incidence risk ratio: 1.5, 95% CI: 1.1-2.1, p = 0.006) and migration of the UVC (incidence risk ratio: 3.5, 95% CI: 1.0-11.5, p = 0.043). CONCLUSION: Adverse events related to insertion occurred in a relatively high percentage of umbilical catheters placed. Increased dwell time remains a significant risk factor for catheter migration and overall failure. Practice change and consideration of risk factors for both individual and overall AE risk are necessary to reduce complications.


Assuntos
Unidades de Terapia Intensiva Neonatal , Veias Umbilicais , Humanos , Estudos Retrospectivos , Recém-Nascido , Feminino , Masculino , Fatores de Risco , Incidência , Artérias Umbilicais , Austrália/epidemiologia , Cateterismo Periférico/efeitos adversos
2.
Clin Exp Allergy ; 53(3): 327-336, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36628520

RESUMO

BACKGROUND: Peanut allergy affects 1%-3% of children in Western countries. Boiling peanuts has been demonstrated to result in a hypoallergenic product that may provide a safer way of inducing desensitization in peanut-allergic patients by first inducing tolerance to boiled peanut. We aimed to assess the efficacy and safety of oral immunotherapy (OIT) using sequential doses of boiled peanuts followed by roasted peanuts for treating peanut allergy in children. METHODS: In this open-label, phase 2, single-arm clinical trial, children aged 6-18 years with a positive history of peanut allergy and positive peanut skin prick test ≥ 8 mm and/or peanut-specific IgE ≥ 15 kU/L at screening underwent OIT involving sequential up-dosing with 12-hour boiled peanut for 12 weeks, 2-hour boiled peanut for 20 weeks and roasted peanut for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. PRIMARY OUTCOME: proportion of children passing open-label oral food challenge involving cumulative administration of 12 roasted peanuts (12 g peanuts; approximately 3000 mg peanut protein) 6-8 weeks after reaching the target maintenance dose. Secondary outcomes included treatment-related adverse events and use of medications for treating allergy symptoms. RESULTS: Between 1 July 2017 and 22 June 2018, 70 participants were enrolled and commenced OIT. Desensitization was successfully induced in 56 of 70 (80%) participants. Withdrawal due to treatment-related adverse events was infrequent (n = 3). Treatment-related adverse events were reported in 43 (61%) participants, corresponding to a rate of 6.58 per 1000 OIT doses. Medication use associated with treatment-related adverse events was infrequent, with rescue epinephrine use reported by three (4%) participants (0.05 per 1000 doses). CONCLUSION: Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitization and is associated with a favourable safety profile.


Assuntos
Hipersensibilidade a Amendoim , Criança , Humanos , Administração Oral , Alérgenos , Arachis/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Adolescente , Masculino , Feminino
3.
Psychol Health Med ; 28(9): 2699-2712, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35373668

RESUMO

The stigma of leprosy will have reduced effects if people cannot reliably perceive it. Two factors impact these perceptions: familiarity and entitativity. One hundred and forty-five participants tested this assertion using an online platform to complete measures of stigma about leprosy as well as measures of familiarity and entitativity. The group of 145 completed the same measures of stigma, entitativity, and familiarity 1 week later. Standard deviations of time 1 and time 2 measures of stigma were used as indices of consistent (reliable) perceptions at the individual level. Results showed partial support for familiarity being positively associated with reliable responding. Moreover, high entitativity scores were associated with greater stigma perceptions at time 1 and time 2. Ongoing research on these indicators may be important in crafting future anti-stigma programs for leprosy.

4.
Aust Crit Care ; 35(1): 89-101, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34088575

RESUMO

INTRODUCTION: Adverse events associated with umbilical catheters include malposition, bloodstream infections, thrombosis, tip migration, and extravasation, resulting in loss of vascular access and increased risk of morbidity and mortality. There is a need for greater understanding of risk factors associated with adverse events to inform safe practice. OBJECTIVES: The aim of the study was to summarise the existing evidence regarding risk factors for umbilical catheter-related adverse events to inform the undertaking of future research. REVIEW METHOD USED: A scoping review of peer-reviewed original research and theses was performed. DATA SOURCES: The US National Library of Medicine National Institutes of Health, Embase, EMcare, and ProQuest Dissertations and Theses were the data sources. REVIEW METHODS: Informed by the Joanna Briggs Institute Reviewer's Manual, all types of original research studies reporting adverse events published in English from 2009 to 2020 were eligible for inclusion. Studies where umbilical artery catheter and umbilical venous catheter data could not be extracted separately were excluded. RESULTS: Searching identified 1954 publications and theses, 1533 were excluded at screening, and 418 were assessed for eligibility at full text. A total of 89 studies met the inclusion criteria. A range of potential risk factors for umbilical arterial and venous catheters were identified. Longer dwell time and prematurity were associated with increased risk of bloodstream infection and thrombosis in cohort studies. Case studies detailed analogous factors such as insertion techniques and lack of catheter surveillance during dwell warrant further investigation. CONCLUSIONS: We identified a vast range of patient, device, and provider risk factors that warrant further investigation. There was a lack of large cohort studies and randomised controlled trials to demonstrate the significance of these risk factors. Improvement in methods to ensure correct catheter tip location and to detect adverse events early is essential. In addition, policy needs to be developed to guide clinicians in catheter surveillance measures to reduce the risk of adverse events.


Assuntos
Infecções Relacionadas a Cateter , Sepse , Trombose , Dispositivos de Acesso Vascular , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Humanos , Fatores de Risco , Trombose/prevenção & controle
5.
Issues Ment Health Nurs ; 42(5): 437-450, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32926796

RESUMO

Promoting health-related campaigns on Twitter has increasingly become a world-wide choice to raise awareness and disseminate health information. Data retrieved from Twitter are now being used to explore how users express their views, attitudes and personal experiences of health-related issues. We focused on Twitter discourse reproduced during Mental Health Awareness Week 2017 by examining 1,200 tweets containing the keywords 'mental health', 'mental illness', 'mental disorders' and '#MHAW'. The analysis revealed 'awareness and advocacy', 'stigmatization', and 'personal experience of mental health/illness' as the central discourses within the sample. The article concludes with some recommendations for future research on digitally-mediated health communication.


Assuntos
Transtornos Mentais , Mídias Sociais , Promoção da Saúde , Humanos , Saúde Mental , Estereotipagem
6.
N Engl J Med ; 376(13): 1245-1255, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28355511

RESUMO

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).


Assuntos
Displasia Broncopulmonar/prevenção & controle , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Docosa-Hexaenoicos/efeitos adversos , Método Duplo-Cego , Emulsões/uso terapêutico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Análise de Regressão
7.
N Engl J Med ; 377(25): 2445-2455, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29081267

RESUMO

BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).


Assuntos
Parto Obstétrico/métodos , Doenças do Prematuro/epidemiologia , Recém-Nascido Prematuro , Mortalidade Perinatal , Cordão Umbilical , Índice de Apgar , Constrição , Feminino , Hematócrito , Humanos , Incidência , Recém-Nascido/sangue , Masculino , Circulação Placentária , Gravidez , Fatores de Tempo
8.
Support Care Cancer ; 28(6): 2949-2957, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31768735

RESUMO

BACKGROUND: Head and neck radiotherapy (H&N RT) patients are at risk for malnutrition following treatment due to dysphagia and alterations in taste quality. This project studied feasibility of a food skills intervention strategy support food preparation, cooking confidence, and individualized dietary choices to support nutritional status in this patient population. METHODS: We piloted a monthly cooking class (called "Eat to Live") from November 2018 to January 2019. Every class included cooking and nutrition domains, organized around a specific meal of the day (i.e., breakfast, lunch, or dinner). Seven participants (4 patients, 3 caregivers) attended at least one class, with four participants (3 patients, 1 caregiver) completing all three classes. Pre- and post-study measures (self-administered questionnaires) assessed changes in cooking behavior, dietary choices, and taste sensation before and after the intervention. RESULTS: Healthful eating scores increased modestly from start to finish of the class (1.5 to 1.7 on a 3-point scale), with averaged patient preference scores for healthy foods increasing incrementally. This took place despite physical taste scores declining across the 3-month study. After completing the class, participants were more likely to select fresh fruits and vegetables, grains, lean cuts of meat, and dairy products. Patients also adopted positive behavioral modifications to their diets, such as eating out at restaurants less often and baking/grilling foods instead of frying. CONCLUSIONS: To our knowledge, this is the first published report on feasibility and patient acceptance of an evidence-based culinary medicine intervention in H&N RT patients. We observed objective improvements in dietary choices and cooking confidence in a small cohort of patient/caregiver dyads. This pilot work justifies follow-on development of a more comprehensive intervention optimized for patient convenience and longitudinal support.


Assuntos
Atitude Frente a Saúde , Culinária , Transtornos de Deglutição/dietoterapia , Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Educação de Pacientes como Assunto/métodos , Lesões por Radiação/dietoterapia , Adulto , Pesquisa Participativa Baseada na Comunidade , Culinária/métodos , Estudos de Viabilidade , Feminino , Frutas , Neoplasias de Cabeça e Pescoço/dietoterapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Nutricional/métodos , Fenômenos Fisiológicos da Nutrição , Aceitação pelo Paciente de Cuidados de Saúde , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Lesões por Radiação/etiologia , Inquéritos e Questionários , Verduras
9.
N Engl J Med ; 374(8): 749-60, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26863265

RESUMO

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Mortalidade Infantil , Lactente Extremamente Prematuro/sangue , Oxigenoterapia/métodos , Oxigênio/sangue , Austrália , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Oximetria , Oxigenoterapia/efeitos adversos , Risco , Reino Unido
10.
Pediatr Res ; 86(6): 738-741, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31351437

RESUMO

BACKGROUND: Non-contact heart rate (HR) and respiratory rate (RR) monitoring is necessary for preterm infants due to the potential for the adhesive electrodes of conventional electrocardiogram (ECG) to cause damage to the epidermis. This study was performed to evaluate the agreement between HR and RR measurements of preterm infants using a non-contact computer vision system with comparison to measurements obtained by the ECG. METHODS: A single-centre, cross-sectional observational study was conducted in a Neonatal Unit. Ten infants and their ECG monitors were videoed using two Nikon cameras for 10 min. HR and RR measurements obtained from the non-contact system were extracted using advanced signal processing techniques and later compared to the ECG readings using Bland-Altman analysis. RESULTS: The non-contact system was able to detect an apnoea when the ECG determined movement as respirations. Although the mean bias between both methods was relatively low, the limits of agreement for HR were -8.3 to 17.4 beats per minute (b.p.m.) and for RR, -22 to 23.6 respirations per minute (r.p.m.). CONCLUSIONS: This study provides necessary data for improving algorithms to address confounding variables common to the neonatal population. Further studies investigating the robustness of the proposed system for premature infants are therefore required.


Assuntos
Inteligência Artificial , Frequência Cardíaca , Recém-Nascido Prematuro , Taxa Respiratória , Telemetria/instrumentação , Algoritmos , Estudos Transversais , Eletrocardiografia , Humanos , Recém-Nascido , Telemetria/métodos
11.
12.
Int J Cancer ; 142(11): 2355-2362, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29313979

RESUMO

While long-term survival rates for early-stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early-stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for our study. After RNA was extracted, the expressions of FPR1 and a reference gene were quantified by an automated one-step Taqman RT-PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off-the-shelf equipment and reagents. Further work is justified to explain the source of this biomarker.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , RNA Mensageiro , Receptores de Formil Peptídeo/genética , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Estudos de Casos e Controles , Comorbidade , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Curva ROC
13.
N Engl J Med ; 372(26): 2481-98, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-26061751

RESUMO

BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).


Assuntos
DNA de Neoplasias/análise , Genes p53 , Glioma/genética , Mutação , Adolescente , Adulto , Idoso , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Análise por Conglomerados , Feminino , Glioblastoma/genética , Glioma/metabolismo , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Análise de Sequência de DNA , Transdução de Sinais
14.
Acc Chem Res ; 49(9): 1957-68, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27536956

RESUMO

Cascade reactions represent a class of ideal organic reactions because they empower efficiency, elegance, and novelty. However, development of cascade reactions remains a daunting task for synthetic chemists. Radicals are known to be well suited for cascade reactions. Compared with widely used carbon-based radicals, nitrogen-based radicals, such as neutral aminyl radicals and protonated aminyl radicals (amine radical cations), are underutilized, although they are behind some notable synthetic methods such as the Hofmann-Löffler-Freytag reaction. The constraint on their usage is generally attributed to the limited number of available stable precursors. Since amine radical cations offer increased reactivity and selectivity in chemical transformations compared with neutral aminyl radicals, their generation is of utmost importance. Recently, a surge of reports has been revealed using visible light photoredox catalysis. It has been demonstrated that amines can act as an electron donor in a reductive quenching cycle while the amine itself is oxidized to the amine radical cation. Although a number of methods exist to generate amine radical cations, the photochemical formation of these species offers many practical advantages. In this Account, we discuss our journey to the development of annulation reactions with various π-bonds and electrophilic addition reactions to alkenes using photogenerated amine radical cations. Various carbocycles and heterocycles are produced by these reactions. In our annulation work, we first show that single electron photooxidation of cyclopropylanilines to the amine radical cations triggers ring opening of the strained carbocycle, producing distonic radical cations. These odd-electron species are shown to react with alkenes and alkynes to yield the corresponding cyclopentanes and cyclopentenes in an overall redox neutral process. Further development of this annulation reaction allows us to achieve the [4 + 2] annulation of cyclobutylanilines with alkynes. In our work on electrophilic addition reactions to alkenes, we reveal that photogenerated amine radical cations are capable of undergoing the electrophilic addition reactions to alkenes to form a variety of indoles and indolines. This chemistry represents a rare oxidative C-N bond-forming reaction using visible light. Conclusions drawn from observational results and proposed mechanisms are outlined in this Account. Additionally, open discussion of our successes and deficiencies in our experiences will give readers helpful insights as to how these species tend to react. The overall utility of photogenerated amine radical cations has yet to reach its full potential. With our current results, we anticipate more new transformations can still be derived from the ring opening processes of cyclopropylanilines and cyclobutylanilines under visible light photocatalysis. Additionally, since utilizing photogenerated amine radical cations in C-N bond-forming reactions has practically been absent in literature, we are confident more new reactions have yet been exploited.


Assuntos
Aminas/química , Cátions/síntese química , Cicloparafinas/síntese química , Radicais Livres/química , Radicais Livres/síntese química , Compostos Heterocíclicos/síntese química , Alcenos/química , Alcinos/química , Aminas/efeitos da radiação , Cátions/química , Ciclização , Cicloparafinas/efeitos da radiação , Luz , Modelos Químicos , Oxirredução , Estereoisomerismo
16.
J Med Libr Assoc ; 104(1): 62-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26807055

RESUMO

A partnership to improve access to health information via an urban public library system was established in St. Louis, Missouri, in 2011. A multiyear project was outlined that included an information needs assessment, a training class for public library staff, information kiosks at library branches for delivering printed consumer health materials, and a series of health-related programming. The partnership evolved to include social service and community organizations to carry out project goals and establish a sustainable program that met the health and wellness interests of the community.


Assuntos
Acesso à Informação , Relações Comunidade-Instituição , Informação de Saúde ao Consumidor/organização & administração , Comportamento Cooperativo , Bibliotecas Médicas/organização & administração , Bibliotecas/organização & administração , Universidades , Cidades , Humanos , Missouri , Estudos de Casos Organizacionais , Avaliação de Programas e Projetos de Saúde
17.
Adv Synth Catal ; 357(10): 2311-2316, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26622221

RESUMO

The synthesis of fused N-arylindolines using visible light photoredox catalysis has been developed. We previously described that photogenerated amine radical cations generate substituted indoles through an intermediate benzylic carbocation. Herein, we expand the application of this chemistry by trapping the benzylic carbocation with tethered heteronucleophiles. The reactivity of the photogenerated benzylic carbocation is explored and applied to a range of substrates with various electronic characters and ring constraints. The method described provides C2 and C3 fused indolines bearing a tetrasubstituted carbon stereocenter with greater than 99:1 diastereoselectivity in moderate to good yields.

18.
Adv Synth Catal ; 356(13): 2831-2837, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26120292

RESUMO

One-step synthesis of carbocycles substituted with amines from simple starting materials remains rare. We recently developed intermolecular [3+2] annulation of cyclopropylanilines with alkenes and alkynes that enable this one-step synthesis. Herein, we report our findings for a fullscale study of the annulation. Significant expansion of the substrate scope for both cyclopropylanilines and alkynes is achieved. A range of structurally diverse carbocycles substituted with amines is prepared.

19.
BMC Nephrol ; 15: 23, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24484613

RESUMO

BACKGROUND: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers. METHODS: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning. RESULTS: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%. CONCLUSIONS: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Rim/fisiologia , Angiografia por Ressonância Magnética/métodos , Artéria Renal/fisiologia , Circulação Renal/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Humanos , Rim/irrigação sanguínea , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin
20.
JAMA Pediatr ; 178(1): 45-54, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983037

RESUMO

Importance: Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain. Objective: To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation. Design, Setting and Participants: This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age. Interventions: Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Main Outcomes and Measures: The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention. Results: Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health. Conclusions and Relevance: In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation. Trial Registration: Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.


Assuntos
Ácidos Docosa-Hexaenoicos , Recém-Nascido Prematuro , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Austrália , Suplementos Nutricionais , Seguimentos , Idade Gestacional
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