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1.
J Pediatr Gastroenterol Nutr ; 79(1): 35-41, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38720566

RESUMEN

OBJECTIVES: Helicobacter pylori rates of eradication to common first-line regimens continue to decline globally. Prescription of the appropriate medication dosage is an important consideration, particularly in the pediatric population due to medication weight-based dosing. Limited data is available on the impact of guideline-recommended weight-based dosing on the successful eradication of H. pylori in children. METHODS: Retrospective study of patients with histologic evidence of H. pylori from two pediatric tertiary care centers in New England. We excluded patients who were not treated or those missing eradication data. We compared the eradication rates of patients prescribed recommended weight-based dosages, duration, and frequency of treatment with those who were not. RESULTS: One hundred forty-four patients were included. The overall eradication rate was 73.6% (106/144). All treatment regimens were properly prescribed for 14 days. There was a high rate of improper weight-based dosing: proton pump inhibitor (PPI) 31.2% (45/144), amoxicillin 31.7% (39/123), metronidazole (MET) 19.4% (12/62), clarithromycin (CLA) 23.9% (22/70), tetracycline 50% (6/12), bismuth 26.1% (6/23). When PPIs were properly weight-dosed, there was a 78.8% eradication rate that dropped to 62.2% with suboptimal dosing (p = 0.036, odds ratio [OR]: 2.26, confidence interval [CI]: 1.04-4.87). When amoxicillin was properly weight-dosed, successful eradication was achieved in 81% versus only 53.8% when improperly dosed (p = 0.002; OR: 3.64, CI: 1.58-8.37). There was no statistically significant impact on eradication rates with improper weight-based dosing of MET, CLA, tetracycline, or bismuth. CONCLUSION: Proper weight-based dosing of amoxicillin and PPI is important for the successful eradication of H. pylori among children in the New England area.


Asunto(s)
Amoxicilina , Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Metronidazol , Inhibidores de la Bomba de Protones , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Estudios Retrospectivos , Helicobacter pylori/efectos de los fármacos , Niño , Femenino , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Adolescente , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Preescolar , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , Quimioterapia Combinada , Tetraciclina/administración & dosificación , Tetraciclina/uso terapéutico , Bismuto/administración & dosificación , Bismuto/uso terapéutico , Peso Corporal , Resultado del Tratamiento
2.
Nature ; 557(7704): 228-232, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29686415

RESUMEN

Most drugs are developed through iterative rounds of chemical synthesis and biochemical testing to optimize the affinity of a particular compound for a protein target of therapeutic interest. This process is challenging because candidate molecules must be selected from a chemical space of more than 1060 drug-like possibilities 1 , and a single reaction used to synthesize each molecule has more than 107 plausible permutations of catalysts, ligands, additives and other parameters 2 . The merger of a method for high-throughput chemical synthesis with a biochemical assay would facilitate the exploration of this enormous search space and streamline the hunt for new drugs and chemical probes. Miniaturized high-throughput chemical synthesis3-7 has enabled rapid evaluation of reaction space, but so far the merger of such syntheses with bioassays has been achieved with only low-density reaction arrays, which analyse only a handful of analogues prepared under a single reaction condition8-13. High-density chemical synthesis approaches that have been coupled to bioassays, including on-bead 14 , on-surface 15 , on-DNA 16 and mass-encoding technologies 17 , greatly reduce material requirements, but they require the covalent linkage of substrates to a potentially reactive support, must be performed under high dilution and must operate in a mixture format. These reaction attributes limit the application of transition-metal catalysts, which are easily poisoned by the many functional groups present in a complex mixture, and of transformations for which the kinetics require a high concentration of reactant. Here we couple high-throughput nanomole-scale synthesis with a label-free affinity-selection mass spectrometry bioassay. Each reaction is performed at a 0.1-molar concentration in a discrete well to enable transition-metal catalysis while consuming less than 0.05 milligrams of substrate per reaction. The affinity-selection mass spectrometry bioassay is then used to rank the affinity of the reaction products to target proteins, removing the need for time-intensive reaction purification. This method enables the primary synthesis and testing steps that are critical to the invention of protein inhibitors to be performed rapidly and with minimal consumption of starting materials.


Asunto(s)
Nanotecnología/métodos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Proteínas/química , Bioensayo , Catálisis , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/antagonistas & inhibidores , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/química , Evaluación Preclínica de Medicamentos , Cinética , Ligandos , Espectrometría de Masas , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/química , Proteínas/antagonistas & inhibidores , Especificidad por Sustrato
3.
BMC Pregnancy Childbirth ; 24(1): 520, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090562

RESUMEN

BACKGROUND: The Safer Baby Bundle (SBB) aimed to reduce stillbirth rates in Australia through improving pregnancy care across five elements; smoking cessation, fetal growth restriction (FGR), decreased fetal movements (DFM), side sleeping in late pregnancy and decision making around timing of birth. We assessed experiences of women and healthcare professionals (HCPs) with antenatal care practices around the five elements. METHODS: A pre-post study design using online surveys was employed to assess change in HCPs awareness, knowledge, and frequency of performing recommended practices (22 in total) and women's experiences of care received related to reducing their chance of stillbirth. Women who had received antenatal care and HCPs (midwives and doctors) at services participating in the SBB implementation program in two Australian states were invited to participate. Surveys were distributed over January to July 2020 (pre) and August to December 2022 (post). Comparison of pre-post responses was undertaken using Fisher's exact, Pearson's chi-squared or Wilcoxon rank-sum tests. RESULTS: 1,225 women (pre-1096/post-129) and 1,415 HCPs (pre-1148/post-267, ≥ 83% midwives) completed the surveys. The frequency of HCPs performing best practice 'all the time' significantly improved post-SBB implementation across all elements including providing advice to women on side sleeping (20.4-79.4%, p < 0.001) and benefits of smoking cessation (54.5-74.5%, p < 0.001), provision of DFM brochure (43.2-85.1%, p < 0.001), risk assessments for FGR (59.2-84.1%, p < 0.001) and stillbirth (44.5-73.2%, p < 0.001). Practices around smoking cessation in general showed less improvement e.g. using the 'Ask, Advise and Help' brief advice model at each visit (15.6-20.3%, p = 0.088). Post-implementation more women recalled conversations about stillbirth and risk reduction (32.2-50.4%, p < 0.001) and most HCPs reported including these conversations in their routine care (35.1-83.0%, p < 0.001). Most HCPs agreed that the SBB had become part of their routine practice (85.0%). CONCLUSIONS: Implementation of the SBB was associated with improvements in practice across all targeted elements of care in stillbirth prevention including conversations with women around stillbirth risk reduction. Further consideration is needed around strategies to increase uptake of practices that were more resistant to change such as smoking cessation support. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the Australian New Zealand Clinical Trials Registry database, ACTRN12619001777189, date assigned 16/12/2019.


Asunto(s)
Atención Prenatal , Cese del Hábito de Fumar , Mortinato , Humanos , Femenino , Mortinato/epidemiología , Embarazo , Atención Prenatal/métodos , Adulto , Australia , Cese del Hábito de Fumar/métodos , Encuestas y Cuestionarios , Retardo del Crecimiento Fetal/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Movimiento Fetal , Paquetes de Atención al Paciente
4.
Aust N Z J Obstet Gynaecol ; 64(1): 63-71, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37551966

RESUMEN

BACKGROUND: The IMPROVE (IMproving Perinatal Mortality Review and Outcomes Via Education) eLearning, developed by the Stillbirth Centre of Research Excellence in partnership with the Perinatal Society of Australia and New Zealand was launched in December 2019. Based on the successful face-to-face program, the eLearning aims to increase availability and accessibility of high-quality online education to healthcare professionals providing care for families around the time of perinatal death, to improve the delivery of respectful and supportive clinical care and increase best practice investigation of perinatal deaths. AIMS: To evaluate participants' reported learning outcomes (change in knowledge and confidence) and overall acceptability of the program. METHODS: Pre- and post-eLearning in-built surveys were collected over two years (Dec. 2019-Nov. 2021), with a mix of Likert and polar questions. Pre- and post-eLearning differences in knowledge and confidence were assessed using McNemar's test. Subgroup analysis of overall acceptability by profession was assessed using Pearson's χ2 . RESULTS: One thousand, three hundred and thirty-nine participants were included. The majority were midwives (80.2%, n = 1074). A significant improvement in knowledge and confidence was shown across all chapters (P < 0.01). The chapter showing the greatest improvement was perinatal mortality audit and classification (21.5% pre- and 89.2% post-education). Over 90% of respondents agreed the online education was relevant, helpful, acceptable, engaging. Importantly, 80.7% of participants considered they were likely to change some aspect of their clinical practice after the eLearning. There was no difference in responses to relevance and acceptability of the eLearning program by profession. CONCLUSIONS: The IMPROVE eLearning is an acceptable and engaging method of delivery for clinical education, with the potential to improve care and management of perinatal deaths.


Asunto(s)
Instrucción por Computador , Educación a Distancia , Muerte Perinatal , Embarazo , Femenino , Humanos , Instrucción por Computador/métodos , Mortinato , Atención a la Salud
5.
Aust N Z J Obstet Gynaecol ; 63(6): 737-745, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37621216

RESUMEN

BACKGROUND: Although many pregnant women accept referrals to stop-smoking support, the uptake of appointments often remains low. AIM: The aim was to review the success of interventions to increase the uptake of external stop-smoking appointments following health professional referrals in pregnancy. MATERIALS AND METHODS: Embase, PubMed, Cochrane Central Register of Controlled Trials, Scopus and CINAHL were searched in February 2023 for studies with interventions to increase the uptake rates of external stop-smoking appointments among pregnant women who smoke. Eligible studies included randomised, controlled, cluster-randomised, quasi-randomised, before-and-after, interrupted time series, case-control and cohort studies. Cochrane tools assessing for bias and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Two before-and-after studies were included, including a combined total of 1996 women who smoked during pregnancy. Both studies had a serious risk of bias, and meta-analysis was not possible due to heterogeneity. One study testing carbon monoxide monitors and opt-out referrals showed increased uptake of external stop-smoking appointments, health professional referrals and smoking cessation rates compared to self-identified smoking status and opt-in referrals. Results were limited in the second study, which used carbon monoxide monitors, urinary cotinine levels and self-disclosed methods to identify the smoking status with opt-out referrals. Only post-intervention data were available on the uptake of appointments to external stop-smoking services. The number of health professional referrals increased, but change in smoking cessation rates was less clear. CONCLUSIONS: There is insufficient evidence to inform practice regarding strategies to increase the uptake of external stop-smoking appointments by women during pregnancy.


Asunto(s)
Cese del Hábito de Fumar , Femenino , Embarazo , Humanos , Monóxido de Carbono , Mujeres Embarazadas , Dispositivos para Dejar de Fumar Tabaco , Fumar
6.
Aust N Z J Obstet Gynaecol ; 63(3): 352-359, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36447356

RESUMEN

BACKGROUND: Combined with perinatal mortality review, neonatal near-miss (NNM) audit has the potential to inform strategies to better prevent adverse perinatal outcomes. Nonetheless, there is lack of standardised definitions of NNM and limited evidence of implementation of NNM audits. AIM: To describe definitions of NNM and assess current approaches and attitudes toward perinatal mortality and morbidity audit. MATERIALS AND METHODS: Online survey from December 2021 to February 2022, with a mix of Likert scales, polar, pool, multi-choice, and open-ended questions, disseminated through national and international organisations to perinatal healthcare workers from high-income countries. RESULTS: One hundred and twenty participants came from Australia (n = 86), New Zealand (n = 18), Canada (n = 7), USA (n = 4), Netherlands (n = 2), other countries (n = 3). Neonatologists (35%), midwives (21.7%), obstetricians (12.5%), neonatal nurse practitioners (11.7%) and others (23.3%) responded. Most respondents thought the main characteristics to define NNM were birth asphyxia needing therapeutic hypothermia (68.3%), unexpected resuscitation at birth (67.5%), need for intubation/chest compression/adrenaline (65.0%) and metabolic acidosis at birth (60.0%). There were 97.5% of participants who considered NNM important for identifying cases for perinatal morbidity audits. However, only 10.0% of their institutions used a NNM definition. Overall, 98.4% of participants considered perinatal mortality and morbidity audits important to prevent adverse outcomes. CONCLUSION: Neonatal near-miss audit is viewed as a valuable tool to reduce adverse neonatal outcomes. There was reasonable consensus that NNM encompassed evidence of birth asphyxia and/or advanced neonatal resuscitation. Data from this international survey identifies a starting point for a consensus definition of NNM, which can be used for perinatal audits to identify opportunities for improvement.


Asunto(s)
Asfixia Neonatal , Potencial Evento Adverso , Muerte Perinatal , Embarazo , Femenino , Recién Nacido , Humanos , Asfixia , Resucitación , Mortalidad Perinatal , Muerte Perinatal/prevención & control , Asfixia Neonatal/prevención & control , Actitud
7.
J Asthma ; 59(10): 2108-2116, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34644225

RESUMEN

OBJECTIVE: Asthma during pregnancy and extremes of body mass index (BMI) are independently associated with adverse pregnancy outcomes but the impact of the two conditions combined are currently unknown. The aim of this study was to determine the contribution of maternal BMI to adverse birth outcomes in pregnancies complicated by asthma. METHODS: The study utilized the routinely collected perinatal data on births at the Mater Mother's Hospital Brisbane, Australia, from January 2008 to December 2019. BMI was grouped as underweight (<18.5), normal weight (18.5-<24.99), overweight (25-29.99), and obese (≥30) and the population split by the presence and absence of maternal asthma. The comparison group was normal BMI, non-asthmatic pregnant women. A modified Poisson regression with robust variance was used to estimate the relative risk. RESULTS: In a retrospective cohort study of 110,057 pregnant women, 17.08% of women had asthma. Asthma and BMI were associated with an increased risk of poor fetal and neonatal outcomes. Asthma significantly increased the risk of stillbirth in underweight [adjusted RR: 2.22 (95% CI: 1.25-3.94] and obese [1.74 (1.11-2.71)]; neonatal death in underweight [3.41 (1.89-6.16)] and obese [2.22 (1.37-3.59)] and perinatal death in underweight [2.34 (1.50-3.66)] and obese [1.92 (1.38-2.67)] women. Admission to the neonatal intensive care unit was increased in neonates of underweight [1.65 (1.44-1.89)] and obese [1.26 (1.14-1.40)] asthmatic women. CONCLUSIONS: Extremes of BMI, specifically underweight and obesity, increased the risk of adverse perinatal outcomes among asthmatic women highlighting the importance of accounting for BMI during pre-conception and pregnancy related management of asthmatic women.


Asunto(s)
Asma , Muerte Perinatal , Asma/complicaciones , Asma/epidemiología , Índice de Masa Corporal , Femenino , Humanos , Recién Nacido , Obesidad/complicaciones , Obesidad/epidemiología , Mortalidad Perinatal , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Delgadez
8.
Aust N Z J Obstet Gynaecol ; 62(3): 358-363, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35243623

RESUMEN

Neonatal near miss (NNM) refers to a newborn who almost died in the neonatal period and is often perceived as part of a spectrum that includes stillbirth and neonatal death. NNM audits might improve recognition of risk factors and substandard care, facilitate benchmarking and inform prevention strategies to improve perinatal outcomes. This review shows that available NNM definitions are inconsistent and vary widely. This is likely to undermine the development of effective prevention strategies and global comparisons. Expert opinion may help reaching a consensus, thus enabling targeting of the appropriate population which would lead to more meaningful data for perinatal audits.


Asunto(s)
Potencial Evento Adverso , Muerte Perinatal , Femenino , Humanos , Mortalidad Infantil , Recién Nacido , Embarazo , Estándares de Referencia , Factores de Riesgo , Mortinato/epidemiología
9.
Bioorg Med Chem Lett ; 47: 128214, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34166782

RESUMEN

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored. Compounds 37 and 41 stood out as leads due to their good potency in IDO1 Hela assay, good IDO1 unbound hWB IC50s, reasonable unbound clearance, and good MRT in rat and dog PK studies.


Asunto(s)
Compuestos Aza/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indoles/farmacología , Animales , Compuestos Aza/síntesis química , Compuestos Aza/química , Perros , Relación Dosis-Respuesta a Droga , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indoles/síntesis química , Indoles/química , Masculino , Estructura Molecular , Ratas , Ratas Wistar , Relación Estructura-Actividad
10.
Environ Res ; 197: 111037, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33781772

RESUMEN

BACKGROUND: Associations between ambient temperature exposure during pregnancy and stillbirth have been reviewed and described in the literature. However, there is no existing review of environmental and epidemiologic methods applied to measure stillbirths resulting from exposure to ambient temperatures during pregnancy. The objective of this study is to systematically review published methods, data sources, and data linkage practices to characterize associations between ambient temperature and stillbirth to inform stillbirth prevention and risk management strategies. METHODS: A systematic review of published studies that assess the association between ambient temperature exposure during pregnancy using any measures or approach and stillbirth was undertaken in Cochrane Library, PubMed, Medline, Scopus, Embase, and Web of Science of studies (2000-2020, inclusive). Selection of studies were assessed by pre-specified eligibility criteria and documented using PRISMA. Citations were managed using EndNote X8 whilst selection, reviewing, and data extraction were performed using Covidence. The screening, selection, and data extraction process consisted of two blind, independent reviews followed by a tertiary independent review. An adapted Critical Appraisal Skills Program (CASP) checklist was used to assess quality and bias. The main findings and characteristics of all studies was extracted and summarized. Where appropriate, a meta-analysis will be performed for measures of association. RESULTS: Among 538 original records, 12 eligible articles were identified that analysed associations between ambient temperature exposure and stillbirth for 42,848 stillbirths among 3.4 million births across seven countries. Varied definitions of stillbirth were reported based on gestational age, birthweight, both, or neither. The overall rate of stillbirth ranged from 1.9 to 38.4 per 1000 among six high-income countries and one low-middle-income country. All study designs were retrospective and included ten cohort studies, three case-crossover studies, and two additional case-control subgroup analysis. Exposure data for ambient temperature was mostly derived from standard municipal or country-level monitors based on weather stations (66.6%) or a forecasting model (16.7%); otherwise, not reported (16.7%). Results were not statistically pooled for a meta-analysis due to heterogeneity of methods and models among included studies. All studies reported associations of increased risk of stillbirth with ambient temperature exposures throughout pregnancy, particularly in late pregnancy. One study estimates 17-19% (PAR) of stillbirths are potentially attributable to chronic exposure to hot and cold ambient temperatures during pregnancy. Overall, risk of stillbirth was observed to increase below 15 °C and above 23.4 °C, where highest risk is above 29.4 °C. CONCLUSION: Exposure to hot and cold temperatures during pregnancy may increase the risk of stillbirth, although a clear causative mechanism remains unknown. Despite lack of causal evidence, existing evidence across diverse settings observed similar effects of increased risk of stillbirth using a variety of statistical and methodological approaches for exposure assessments, exposure windows, and data linkage. Managing exposure to ambient temperatures during pregnancy could potentially decrease risk of stillbirth, particularly among women in low-resource settings where access to safe antenatal and obstetric care is challenging. To fully understand the effects or dose-response relationship of maternal exposure to ambient temperatures and stillbirth, future studies should focus on biological mechanisms and contributing factors in addition to improving measurement of ambient temperature exposure.


Asunto(s)
Mortinato , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Mortinato/epidemiología , Temperatura
11.
Aust N Z J Obstet Gynaecol ; 61(5): 675-683, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34096613

RESUMEN

BACKGROUND: The Safer Baby Bundle (SBB) eLearning is an online education module that addresses practice gaps in stillbirth prevention in Australia. It provides healthcare professionals with evidence-based resources for: smoking cessation; fetal growth restriction; decreased fetal movements; maternal safe going-to-sleep position; and timing of birth for women with risk factors for stillbirth. AIMS: To determine whether participants' reported knowledge and confidence in providing care designed to reduce stillbirth changed following completion of the module. To assess the module's suitability and acceptability, and participants' reported likelihood to change practice. MATERIALS AND METHODS: In-built surveys undertaken pre- and post-eLearning module assessed participant knowledge and confidence, module suitability and acceptability, and likelihood of practice change using Likert items. Responses were dichotomised. Differences pre- and post-module were tested using McNemar's test and differences by profession were examined using descriptive statistics and Pearson's χ2 test. RESULTS: Between 15 October 2019 and 2 November 2020, 5223 participants across Australia were included. Most were midwives (82.0%), followed by student midwives (4.6%) and obstetricians (3.3%). Reported knowledge and confidence improved in all areas (P < 0.001). Post-module 96.7-98.9% 'agreed' they had a sound level of knowledge and confidence across all elements of the SBB. Over 95% of participants agreed that the module was helpful and relevant, well organised, and easy to access and use. Eighty-eight percent reported they were likely to change some aspect of their clinical practice. CONCLUSIONS: The SBB eLearning module is a valuable education program that is well-received and likely to result in improvements in practice.


Asunto(s)
Educación a Distancia , Enfermedades Fetales , Australia , Femenino , Humanos , Lactante , Embarazo , Mortinato , Encuestas y Cuestionarios
12.
Chembiochem ; 21(13): 1905-1910, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32003101

RESUMEN

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.


Asunto(s)
Cardiomiopatías/prevención & control , Familia 1 del Citocromo P450/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Animales Modificados Genéticamente , Cardiomiopatías/inducido químicamente , Cardiomiopatías/patología , Familia 1 del Citocromo P450/antagonistas & inhibidores , Familia 1 del Citocromo P450/genética , Modelos Animales de Enfermedad , Doxorrubicina/toxicidad , Insuficiencia Cardíaca , Mutagénesis , Fenotipo , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/metabolismo , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Relación Estructura-Actividad , Pez Cebra , Proteínas de Pez Cebra/antagonistas & inhibidores , Proteínas de Pez Cebra/genética
13.
FASEB J ; 33(1): 584-605, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30036086

RESUMEN

Repair after damage is essential for tissue homeostasis. Postmenstrual endometrial repair is a cyclical manifestation of rapid, scar-free, tissue repair taking ∼3-5 d. Skin repair after wounding is slower (∼2 wk). In the case of chronic wounds, it takes months to years to restore integrity. Herein, the unique "rapid-repair" endometrial environment is translated to the "slower repair" skin environment. Menstrual fluid (MF), the milieu of postmenstrual endometrial repair, facilitates healing of endometrial and keratinocyte "wounds" in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin reconstruct model, and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins: migration inhibitory factor, neutrophil gelatinase-associated lipocalin, follistatin like-1, chemokine ligand-20, and secretory leukocyte protease inhibitor were selected for further investigation. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration. Translation of these and other MF factors into a migration-inducing treatment paradigm could provide novel treatments for tissue repair.-Evans, J., Infusini, G., McGovern, J., Cuttle, L., Webb, A., Nebl, T., Milla, L., Kimble, R., Kempf, M., Andrews, C. J., Leavesley, D., Salamonsen, L. A. Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repair.


Asunto(s)
Endometrio/citología , Queratinocitos/citología , Menstruación/metabolismo , Proteoma/metabolismo , Piel/citología , Cicatrización de Heridas , Animales , Adhesión Celular , Movimiento Celular , Proliferación Celular , Endometrio/metabolismo , Femenino , Humanos , Queratinocitos/metabolismo , Proteómica , Piel/metabolismo , Porcinos
14.
Wound Repair Regen ; 25(5): 792-804, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28857337

RESUMEN

Deep dermal burn injuries require extensive medical care; however, the water temperatures and durations of exposure that result in a severe scald injury are unknown. This study used a porcine burn model to investigate the time and temperature threshold for clinically relevant deep dermal injuries for both immersion (long duration) and spill/splash (short duration) scald events. Scald wounds were created on the flanks of anaesthetized juvenile large White pigs (27 kg). Acute tissue injury evaluations performed at 1 hour and days 1, 3, and 7 postburn (16 pigs) included: wound examination, biopsies, and laser Doppler imaging. Up to 20 burn combinations were tested including: 50-60 °C water for 1-10 minutes (immersion); and 60-90 °C water for 5 seconds (spill/splash). Burn conditions demonstrating mid-to-deep dermal damage histologically were followed for 21 days to assess time to reepithelialize (eight pigs). Histologically, depth of damage increased until day 3 postburn. Damage to ≥75% of the depth of dermis was associated with burns taking longer than 3 weeks to fully reepithelialize. For spill/splash (5 seconds) scalds, water at ≥75 °C showed damage to mid-dermis or deeper by day 3; however, only burns from water ≥85 °C were not reepithelialized by day 21. For immersion scalds of equivalent duration, water at 55 °C caused significantly deeper dermal damage than 50 °C (p < 0.05) at day 3. Immersion scalds that were not fully reepithelialized by day 21 included 50 °C for >10 minutes, 55 °C for 5 minutes, 60 °C for 60 seconds, and 70 °C for > 15 seconds. This research provides valuable evidence-based injury prediction data, which can be used to inform future burn injury prevention guidelines/legislation to reduce the risk of severe scald injuries and support medicolegal opinions for cases where an inflicted mechanism of injury is alleged.


Asunto(s)
Quemaduras/patología , Dermis/patología , Calor/efectos adversos , Cicatrización de Heridas , Animales , Modelos Animales de Enfermedad , Repitelización , Porcinos , Factores de Tiempo , Índices de Gravedad del Trauma , Agua
15.
Int Wound J ; 14(6): 1199-1212, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28736990

RESUMEN

There are many porcine burn models that create burns using different materials (e.g. metal, water) and different burn conditions (e.g. temperature and duration of exposure). This review aims to determine whether a pooled analysis of these studies can provide insight into the burn materials and conditions required to create burns of a specific severity. A systematic review of 42 porcine burn studies describing the depth of burn injury with histological evaluation is presented. Inclusion criteria included thermal burns, burns created with a novel method or material, histological evaluation within 7 days post-burn and method for depth of injury assessment specified. Conditions causing deep dermal scald burns compared to contact burns of equivalent severity were disparate, with lower temperatures and shorter durations reported for scald burns (83°C for 14 seconds) compared to contact burns (111°C for 23 seconds). A valuable archive of the different mechanisms and materials used for porcine burn models is presented to aid design and optimisation of future models. Significantly, this review demonstrates the effect of the mechanism of injury on burn severity and that caution is recommended when burn conditions established by porcine contact burn models are used by regulators to guide scald burn prevention strategies.


Asunto(s)
Quemaduras/fisiopatología , Calor/efectos adversos , Animales , Modelos Animales de Enfermedad , Índice de Severidad de la Enfermedad , Sus scrofa , Porcinos
16.
Gastroenterol Hepatol (N Y) ; 20(8): 469-476, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39205950

RESUMEN

Helicobacter pylori infection affects over half of the world's population and is a global health concern because it contributes to chronic and fatal gastrointestinal disorders, including peptic ulcer disease and gastric cancer. The escalating prevalence of antibiotic-resistant strains of H pylori necessitates a change in management. The conventional strategy of empiric-based treatments is becoming increasingly ineffective in both adult and pediatric populations; rates of eradication to common first-line regimens remain suboptimal and continue to decline. Culture-based susceptibility testing for H pylori has been underutilized and challenging to incorporate into practice. Next-generation sequencing (NGS), which can identify the genetic biomarkers that predict antimicrobial resistance and susceptibility patterns, offers a promising alternative. NGS may enable clinicians to tailor individual treatment regimens and contribute to epidemiologic surveillance across populations. As NGS technology advances and becomes more accessible, its integration into routine clinical practice holds the potential to transform H pylori management strategies and improve patient outcomes. This article reviews the literature describing antimicrobial resistance patterns in adult and pediatric practice in the United States and provides practical guidance on the current role of NGS in the management of H pylori.

17.
J Obstet Gynecol Neonatal Nurs ; 53(5): 572-580, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39030936

RESUMEN

OBJECTIVE: To evaluate the frequency and interrelationships among neonatal near miss (NNM) criteria and the anticipated workload for audits in high-income countries. DESIGN: Observational retrospective descriptive study. SETTING: Tertiary maternal and neonatal units at Mater Mothers' Hospital, Brisbane, Queensland, Australia. PARTICIPANTS: Cases of stillbirths (n = 483), neonatal deaths (n = 203), and live births (n = 66,353) from January 2016 to July 2022 (N = 67,039). METHODS: We identified eight prespecified NNM criteria nominated by perinatal experts. Primary outcomes were NNM frequency, their interrelationships, and related workload. We used descriptive statistics and analysis of variance and considered p < .05 significant. RESULTS: We found 2,243 unique NNM cases (33.7/1,000 live births). The NNM ratio per 1,000 live births according to each of the eight criteria were: unplanned resuscitation at birth (25.09/1,000 live births), birth asphyxia needing surveillance for hypoxic ischemic encephalopathy (8.46/1,000 live births), metabolic acidosis at birth (8.04/1,000 live births), advanced resuscitation at birth (3.68/1,000 live births), seizures and/or stroke (0.96/1,000 live births), severe intraventricular hemorrhage and/or cerebellar hemorrhage (0.95/1,000 live births), moderate to severe hypoxic ischemic encephalopathy (0.9/1,000 live births), and severe birth trauma (0.44/1,000 live births). Almost one third of NNM cases met more than one criterion. Anticipated workload for monthly NNM audits varied from 0.04 to 2.8 cases per 1,000 live births. CONCLUSION: Different sets of NNM criteria considerably alter the frequency of NNMs and the anticipated workload for NNM audits. Their interrelationships are likely attributable to the fact that some of the criteria are risk factors for or are part of the causal pathway for other NNM criteria. These findings can assist with the determination of a pragmatic NNM definition considering the feasibility of NNM audits in high-income countries.


Asunto(s)
Potencial Evento Adverso , Humanos , Estudios Retrospectivos , Recién Nacido , Femenino , Embarazo , Queensland/epidemiología , Potencial Evento Adverso/estadística & datos numéricos , Masculino , Lactante , Mortalidad Infantil/tendencias , Mortinato/epidemiología , Adulto
18.
Women Birth ; 36(5): 446-453, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36858915

RESUMEN

BACKGROUND: The Still Six Lives campaign aimed to increase awareness of stillbirth among Australian women and educate people about three modifiable behaviours that pregnant women could take to reduce the risk of stillbirth. The campaign used earned media, digital advertising and social media. AIM: The aim of this study is to evaluate the impact of the campaign on Australian women's awareness of stillbirth, and knowledge of the three modifiable behaviours. METHODS: The study collected process evaluation data about campaign implementation from digital platforms. The impact evaluation comprised of two components: a three-wave community survey of Australian women aged 18-50 years old, and a pre-post cross-sectional maternity service survey of pregnant women. RESULTS: The campaign gained significant reach, including 2,974,375 completed video views and 910,000 impressions via social media influencers. The community surveys had 1502 participants at baseline, 1517 mid-campaign and 1598 post-campaign. Participants were slightly more likely to have encountered messages about stillbirth after the campaign (aOR 1.30, 95% CI 1.09-1.55). There were increases in awareness of each behaviour after the campaign: be aware of baby's movements (aOR 1.26, 95% CI 1.08-1.47), quit smoking (aOR 1.27, 95% CI 1.10-1.47) and going-to-sleep on side (aOR 1.55, 95% CI 1.32-1.82). The antenatal clinic survey had 296 participants at baseline and 178 post-campaign. Post-campaign, there was an increased likelihood that women were aware of side-sleeping (aOR 3.11, 95% CI 1.74-5.56). CONCLUSIONS: The national campaign demonstrated some evidence of change in awareness of three modifiable behaviours that can reduce the risk of stillbirth.


Asunto(s)
Promoción de la Salud , Mortinato , Femenino , Humanos , Embarazo , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Australia/epidemiología , Mortinato/epidemiología , Estudios Transversales , Publicidad
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