Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.806
Filtrar
Más filtros

Intervalo de año de publicación
1.
Diabet Med ; : e15379, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881382

RESUMEN

BACKGROUND AND AIMS: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. MATERIALS AND METHODS: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI-SYM), DD (DDS-17) and depressive symptoms (PHQ-9). RESULTS: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2-5.6] and with depressive symptoms (OR: 5.9 [3.5-9.9]). CONCLUSIONS: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh.

2.
J Neurooncol ; 166(3): 493-501, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38285244

RESUMEN

BACKGROUND: Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH-) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH- was combined with temozolomide and radiotherapy. As P-AscH- relies on iron-dependent mechanisms, this study aimed to assess the predictive potential of both molecular and imaging-based iron-related markers to enhance the personalization of P-AscH- therapy in glioblastoma participants. METHODS: Participants (n = 55) with newly diagnosed glioblastoma were enrolled in a phase 2 clinical trial conducted at the University of Iowa (NCT02344355). Tumor samples obtained during surgical resection were processed and stained for transferrin receptor and ferritin heavy chain expression. A blinded pathologist performed pathological assessment. Quantitative susceptibility mapping (QSM) measures were obtained from pre-radiotherapy MRI scans following maximal safe surgical resection. Circulating blood iron panels were evaluated prior to therapy through the University of Iowa Diagnostic Laboratory. RESULTS: Through univariate analysis, a significant inverse association was observed between tumor transferrin receptor expression and overall and progression-free survival. QSM measures exhibited a significant, positive association with progression-free survival. Subjects were actively followed until disease progression and then were followed through chart review or clinical visits for overall survival. CONCLUSIONS: This study analyzes iron-related biomarkers in the context of P-AscH- therapy for glioblastoma. Integrating molecular, systemic, and imaging-based markers offers a multifaceted approach to tailoring treatment strategies, thereby contributing to improved patient outcomes and advancing the field of glioblastoma therapy.


HIGHLIGHTS: Pharmacological ascorbate shows significant promise to enhance glioblastoma clinical outcomes. Transferrin receptor and ferritin heavy chain expression represent potential molecular markers to predict pharmacological ascorbate treatment response. Quantitative Susceptibility Mapping is an MRI technique that can serve as a non-invasive marker of iron metabolism to evaluate progression-free survival. Systemic iron metabolic markers are readily available diagnostic tests that can potentially be used to prognosticate overall survival.


Asunto(s)
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/tratamiento farmacológico , Hierro , Temozolomida/uso terapéutico , Antineoplásicos/uso terapéutico , Biomarcadores , Receptores de Transferrina , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/cirugía
3.
Int J Behav Nutr Phys Act ; 21(1): 40, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627708

RESUMEN

BACKGROUND: Actigraphy is often used to measure sleep in pediatric populations, despite little confirmatory evidence of the accuracy of existing sleep/wake algorithms. The aim of this study was to determine the performance of 11 sleep algorithms in relation to overnight polysomnography in children and adolescents. METHODS: One hundred thirty-seven participants aged 8-16 years wore two Actigraph wGT3X-BT (wrist, waist) and three Axivity AX3 (wrist, back, thigh) accelerometers over 24-h. Gold standard measures of sleep were obtained using polysomnography (PSG; Embletta MPRPG, ST + Proxy and TX Proxy) in the home environment, overnight. Epoch by epoch comparisons of the Sadeh (two algorithms), Cole-Kripke (three algorithms), Tudor-Locke (four algorithms), Count-Scaled (CS), and HDCZA algorithms were undertaken. Mean differences from PSG values were calculated for various sleep outcomes. RESULTS: Overall, sensitivities were high (mean ± SD: 91.8%, ± 5.6%) and specificities moderate (63.8% ± 13.8%), with the HDCZA algorithm performing the best overall in terms of specificity (87.5% ± 1.3%) and accuracy (86.4% ± 0.9%). Sleep outcome measures were more accurately measured by devices worn at the wrist than the hip, thigh or lower back, with the exception of sleep efficiency where the reverse was true. The CS algorithm provided consistently accurate measures of sleep onset: the mean (95%CI) difference at the wrist with Axivity was 2 min (-6; -14,) and the offset was 10 min (5, -19). Several algorithms provided accurate measures of sleep quantity at the wrist, showing differences with PSG of just 1-18 min a night for sleep period time and 5-22 min for total sleep time. Accuracy was generally higher for sleep efficiency than for frequency of night wakings or wake after sleep onset. The CS algorithm was more accurate at assessing sleep period time, with narrower 95% limits of agreement compared to the HDCZA (CS:-165 to 172 min; HDCZA: -212 to 250 min). CONCLUSION: Although the performance of existing count-based sleep algorithms varies markedly, wrist-worn devices provide more accurate measures of most sleep measures compared to other sites. Overall, the HDZCA algorithm showed the greatest accuracy, although the most appropriate algorithm depends on the sleep measure of focus.


Asunto(s)
Actigrafía , Sueño , Niño , Adolescente , Humanos , Reproducibilidad de los Resultados , Polisomnografía , Algoritmos
4.
Paediatr Respir Rev ; 49: 9-13, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37696714

RESUMEN

AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.


Asunto(s)
Distrofia Muscular de Duchenne , Niño , Humanos , Distrofia Muscular de Duchenne/complicaciones , Hipoventilación , Estudios Transversales , Estudios Prospectivos , Espirometría , Sueño
5.
Community Dent Health ; 41(2): 111-116, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38373221

RESUMEN

OBJECTIVES: Adults who have learning disabilities are a vulnerable group, little is known about their oral health and how this affects their quality of life. The aims of this secondary analysis of data from the 2009 Adult Dental Health Survey (ADHS) were to describe the oral health status of adults with learning disabilities, determine if severity of learning disability is associated with oral health and identify some of the methodological complexities of working with this population. The survey yields the most recent representative data on the oral health of adults with learning disabilities in England and importantly, contains information about oral health related quality of life (OHRQoL). BASIC RESEARCH DESIGN: Secondary analysis of data from a supplemental survey of adults with learning disabilities collected alongside the 2009 ADHS. PARTICIPANTS: 607 participants with a diagnosed learning disability aged 18 years and over. RESULTS: Adults with learning disabilities had similar levels of active dental caries, fewer natural teeth, and fewer fillings than comparable participants from the general population. Self-reported oral and general health were worse for adults with learning disabilities than the general population. Possible associations between the severity of learning disability and the numbers of decayed, missing or filled teeth were identified. However, large amounts of missing data limited the analysis. CONCLUSIONS: There are important questions relating to the accessibility of existing self-reported oral health questionnaires and the reliability of proxy-reported questions about OHRQoL that should be addressed to give a fuller picture of the oral health of adults with learning disabilities.


Asunto(s)
Encuestas de Salud Bucal , Discapacidades para el Aprendizaje , Salud Bucal , Humanos , Adulto , Discapacidades para el Aprendizaje/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Adulto Joven , Calidad de Vida , Adolescente , Inglaterra/epidemiología , Caries Dental/epidemiología , Anciano
6.
Phys Rev Lett ; 130(21): 212701, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295108

RESUMEN

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.


Asunto(s)
Helio , Hidrógeno , Modelos Estadísticos , Neutrones
7.
J Nucl Cardiol ; 30(1): 193-200, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36417121

RESUMEN

BACKGROUND: Radionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters. METHODS: A retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated. RESULTS: An improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups. CONCLUSIONS: A significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.


Asunto(s)
Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Estudios Retrospectivos , Volumen Sistólico , Ventriculografía con Radionúclidos , Imagen de Acumulación Sanguínea de Compuerta
8.
Adv Exp Med Biol ; 1438: 167-172, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37845456

RESUMEN

We present here the initial development of a novel algorithm based on broadband near-infrared spectroscopy (bNIRS) data to estimate the changes in brain temperature (BT) in neonates. We first explored the validity of the methodology on a simple numerical phantom and reported good agreements between the theoretical and retrieved values of BT and hemodynamic parameters changes, which are the parameters usually targeted by bNIRS. However, we noted an underestimation of the absolute values of temperature and haemoglobins' concentration changes when large variations of tissue saturation were induced, probably due to a crosstalk between the species in this specific case. We then tested this methodology on data acquired on 2 piglets during a protocol that induces seizures. We showed that despite a decrease in rectal temperature (RT) over time (-0.1048 °C 1.5 h after seizure induction, 95% CI: -0.1035 to -0.1061 °C), BT was raising (0.3122 °C 1.5 h after seizure induction, 95% CI: 0.3207 to 0.3237 °C). We also noted that the piglet displaying the largest decrease in RT also displays the highest increase in BT, which could be a marker of the severity of the seizure induced brain injury. These initial results are encouraging and show that having access to the changes in BT non-invasively could help to better understand the impact of BT on injury severity and to improve the current cooling methodologies in the neonatal neurocritical care following neonatal encephalopathy.


Asunto(s)
Lesiones Encefálicas , Espectroscopía Infrarroja Corta , Animales , Porcinos , Temperatura , Encéfalo/diagnóstico por imagen , Convulsiones
9.
Community Dent Health ; 40(1): 53-59, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36696488

RESUMEN

OBJECTIVE: Rapid review of the literature on strategies to increase participation rates in school-based epidemiological surveys. BASIC RESEARCH DESIGN: Rapid review. MEDLINE and Embase databases were searched for articles written in English from 2000 onwards. Synthesised evidence and primary research were included as data sources from peer reviewed journals and reports. INTERVENTIONS: Any strategy aiming to increase participation in school-based health surveys. The comparator was usual procedure or an alternative strategy to increase participation. MAIN OUTCOME MEASURES: Primary outcomes included participation and consent rates. Secondary outcomes were feasibility, acceptability and adverse effects. RESULTS: The search identified 591 unique records, of which 587 were excluded. Four studies were suitable for inclusion, including one systematic review, one randomised controlled trial, one cross-sectional study and one retrospective analysis. Based on very low certainty evidence, recommendations for maximising participation rates in one systematic review of US studies included: promoting the survey to school staff, parents and students; disseminating study information using direct rather than mediated methods; offering incentives to schools, staff and participants; following up non-responders; and employing a research team member to co-ordinate and monitor recruitment. However, UK studies found that different strategies did not increase participation more than that achieved by a standard approach (delivery of covering letter/consent forms via the child with no follow-up of non-responders). CONCLUSION: Given the lack of evidence of effectiveness of alternative strategies in the UK, additional measures beyond existing standard approaches for active consent cannot be recommended.


Asunto(s)
Encuestas Epidemiológicas , Instituciones Académicas , Estudiantes , Niño , Humanos , Estudios Transversales , Padres , Estudios Retrospectivos , Salud Bucal , Consentimiento Paterno
10.
J Clin Monit Comput ; 37(5): 1369-1377, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36967391

RESUMEN

Repeated administration of high doses of propofol to patients with treatment-resistant depression (TRD) has been shown to produce antidepressant effects in small clinical trials. These effects can be elicited when the patient's EEG burst-suppression ratio (BSR) is maintained at 70-90% for 15 min in repeated treatments. This deep anesthesia domain lies beyond the range of current propofol pharmacokinetic/pharmacodynamic (PK/PD) models. In this study, we adapt the Eleveld model for use at deep anesthesia levels with a BSR endpoint, with the goal of aiding the estimation of the dosage of propofol needed to achieve 70-90% BSR for 15 min. We test the ability of the adapted model to predict BSR for these treatments. Twenty participants underwent 6-9 treatments of high doses of propofol (5-9 of which were included in this analysis) for a total of 115 treatments. To adapt the Eleveld model for this endpoint, we optimized the model parameters Ke0, γ and Ce50. These parameters were then used in the adapted model to estimate second-by-second BSR for each treatment. Estimated BSR was compared with observed BSR for each treatment of each participant. Median absolute performance error (MdAPE) between the estimated and observed BSR (25th-75th percentile) was 6.63 (3.79-12.96) % points and 8.51 (4.32-16.74) % between the estimated and observed treatment duration. This predictive performance is statistically significantly better at predicting BSR compared with the standard Eleveld model at deep anesthesia levels. Our adapted Eleveld model provides a useful tool to aid dosing propofol for high-dose anesthetic treatments for depression.


Asunto(s)
Propofol , Humanos , Anestésicos Intravenosos , Depresión/tratamiento farmacológico , Infusiones Intravenosas
11.
Illn Crises Loss ; 31(3): 558-575, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38603162

RESUMEN

The aim of this study was to explore children's experience and responses to the Covid-19 pandemic through their illustrations and short narrations. During October 2020 and January 2021 data was collected from thirteen children aged 9-10 years old in a primary school in the North-West of England. Children were asked to draw their thoughts and feelings about the pandemic and to write a short narration to accompany the drawing. Thematic analysis of data revealed that during the pandemic children at this age have an understanding of death, experience death anxiety and are able to use creative expression to facilitate meaning of the impact of lockdown on their lives such as feeling isolated, lonely, sad and bored. Creative expression also facilitated adaptive coping mechanisms derived from being able to spend more time with family. The data on primary school children is part of a larger study which involved surveys and interviews with children aged 12-16 years in secondary schools.

12.
Illn Crises Loss ; 31(1): 175-199, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36605778

RESUMEN

Background: The COVID-19 pandemic has resulted in many changes to the lives of children and young people. Our aim is to explore the impact of the pandemic on the mental health of children and young people (ages 5-21). Methods: The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines was used to report the findings of this rapid review. Results: Children and young people are potentially very vulnerable to the emotional impact of traumatic events that disrupt their daily lives. Key areas of concern include: Death Anxiety and Fear of Infection; lack of social interaction and loss of routine. Conclusions: Despite some early and responsive studies, the evidence base for pandemic impact on children and young people is very limited. Such evidence is urgently needed if adequate and responsive services, that can mitigate the long-term impact of the pandemic for children and young people can be established.

13.
J Nucl Cardiol ; 29(2): 581-589, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-32748278

RESUMEN

BACKGROUND: Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. METHODS: In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. RESULTS: Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. CONCLUSIONS: The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.


Asunto(s)
Neoplasias de la Mama , Cardiopatías , Disfunción Ventricular Izquierda , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad , Femenino , Humanos , Ventriculografía con Radionúclidos , Estudios Retrospectivos , Medición de Riesgo , Volumen Sistólico , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda
14.
Med Teach ; 44(4): 418-424, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34762549

RESUMEN

INTRODUCTION: Objective Structured Clinical Examinations (OSCE) are used to assess clinical skills. We investigated how exit OSCEs changed in Australian medical schools in response to the COVID-19 pandemic. MATERIALS AND METHODS: The lead ACCLAiM assessment academic from 12 eligible Australian medical school members of the Australian Collaboration for Clinical Assessment in Medicine (ACCLAiM) received a 45-item semi-structured online questionnaire. RESULTS: All schools (12/12) responded. Exit OSCEs were not used by one school in 2019, and 3/11 schools in 2020. Of eight remaining schools, four reduced station numbers and testing time. The minimum OSCE testing time decreased from 64 min in 2019 to 54 min in 2020. Other modifications included: a completely online 'e-OSCE' (n = 1); hybrid delivery (n = 4); stations using: videos of patient encounters (n = 3), telephone calls (n = 2), skill completion without face-to-face patient encounters (n = 3). The proportion of stations involving physical examination reduced from 33% to 17%. Fewer examiners were required, and university faculty staff formed a higher proportion of examiners. CONCLUSIONS: All schools changed their OSCEs in 2020 in response to COVID-19. Modifications varied from reducing station numbers and changing delivery methods to removing OSCE and complete assessment re-structuring. Several innovative methods of OSCE delivery were implemented to preserve OSCE validity and reliability whilst balancing feasibility.


Asunto(s)
COVID-19 , Facultades de Medicina , Australia/epidemiología , COVID-19/epidemiología , Competencia Clínica , Evaluación Educacional , Humanos , Pandemias , Examen Físico , Reproducibilidad de los Resultados
15.
J Sports Sci ; 40(8): 934-949, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35220909

RESUMEN

In the research concerning rational emotive behaviour therapy (REBT) in sport and exercise, irrational beliefs are proposed as a risk factor for health. Concurrent to this, researchers have also indicated that autonomous and controlled motivation, as proposed in organismic integration theory could, together with irrational beliefs, determine individual health. However, research is yet to align irrational beliefs and motivation, and explore how this alignment relates to mental health. The present two study paper identifies individual subgroups, drawn from data concerning irrational beliefs, motivation, and health (psychological distress, and physical health), in a sample of exercisers (study 1) and student athletes (study 2). We examined the latent profile structure of irrational beliefs and motivation, and how these latent profiles relate to psychological distress (studies 1 and 2), and physical health (study 2). Results indicate a two class profile whereby class 1 is characterised by high irrational beliefs, low self-determined motivation, and poor health outcomes. Class 2 is characterised by low irrational beliefs, high self-determined motivation, and better health outcomes. The findings are discussed in relation to the theoretical implications for REBT and organismic integration theory, and the practical implications for key stakeholders in the health of exercise participants and athletes.


Asunto(s)
Motivación , Distrés Psicológico , Atletas/psicología , Humanos , Salud Mental , Autonomía Personal
16.
Acute Med ; 21(4): 205-206, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36809453

RESUMEN

Overuse of corticosteroids is an important problem not only in asthma but also the management of other airways diseases including bronchiectasis and COPD and results in associated risks of serious side effects and irreversible harm. We report a pilot using an in-reach solution to review patients, optimise their care and facilitate early discharge. We discharged >20% of our patients immediately, which is potentially a significant reduction in hospital bed use and, most importantly, through this approach we were able to establish early diagnosis and reduce inappropriate oral corticosteroid use.


Asunto(s)
Corticoesteroides , Asma , Humanos , Corticoesteroides/efectos adversos , Progresión de la Enfermedad , Alta del Paciente , Grupo de Atención al Paciente
17.
Mol Psychiatry ; 25(11): 3106, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30705428

RESUMEN

In the original version of this article, affiliation 3 was given as: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong, University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China". This has now been corrected to: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China".Additionally in the 'Data availability' section an incorrect accession code was given. The accession code has now been changed from 'PDB A9X (AnkG:GABARAPL)' to 'PDB 6A9X (AnkG:GABARAP)'.These errors have been corrected in both the PDF and HTML versions of the Article.

18.
Mol Psychiatry ; 25(11): 2800-2817, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-30504823

RESUMEN

GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize cell surface GABAA receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.


Asunto(s)
Ancirinas/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Vías Nerviosas , Prosencéfalo/citología , Prosencéfalo/metabolismo , Adulto , Anciano , Animales , Ancirinas/genética , Trastorno Bipolar/genética , Trastorno Bipolar/metabolismo , Células Cultivadas , Femenino , Neuronas GABAérgicas/metabolismo , Humanos , Masculino , Ratones , Persona de Mediana Edad , Sinapsis/metabolismo , Adulto Joven
19.
Ultrasound Obstet Gynecol ; 58(4): 597-602, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34090308

RESUMEN

OBJECTIVE: 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell-free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples. METHODS: In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in-situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0-Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype. RESULTS: The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2-80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5-100%)). CONCLUSIONS: The results of this large-scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0-0.5%) false-positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false-positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Síndrome de DiGeorge/diagnóstico , Pruebas de Detección del Suero Materno/estadística & datos numéricos , Adulto , Síndrome de DiGeorge/embriología , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Análisis por Micromatrices , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Sensibilidad y Especificidad , Método Simple Ciego
20.
Perfusion ; 36(4): 421-428, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32820708

RESUMEN

INTRODUCTION: Fevers following decannulation from veno-venous extracorporeal membrane oxygenation often trigger an infectious workup; however, the yield of this workup is unknown. We investigated the incidence of post-veno-venous extracorporeal membrane oxygenation decannulation fever as well as the incidence and nature of healthcare-associated infections in this population within 48 hours of decannulation. METHODS: All patients treated with veno-venous extracorporeal membrane oxygenation for acute respiratory failure who survived to decannulation between August 2014 and November 2018 were retrospectively reviewed. Trauma patients and bridge to lung transplant patients were excluded. The highest temperature and maximum white blood cell count in the 24 hours preceding and the 48 hours following decannulation were obtained. All culture data obtained in the 48 hours following decannulation were reviewed. Healthcare-associated infections included blood stream infections, ventilator-associated pneumonia, and urinary tract infections. RESULTS: A total of 143 patients survived to decannulation from veno-venous extracorporeal membrane oxygenation and were included in the study. In total, 73 patients (51%) were febrile in the 48 hours following decannulation. Among this cohort, seven healthcare-associated infections were found, including five urinary tract infections, one blood stream infection, and one ventilator-associated pneumonia. In the afebrile cohort (70 patients), four healthcare-associated infections were found, including one catheter-associated urinary tract infection, two blood stream infections, and one ventilator-associated pneumonia. In all decannulated patients, the majority of healthcare-associated infections were urinary tract infections (55%). No central line-associated blood stream infections were identified in either cohort. When comparing febrile to non-febrile cohorts, there was a significant difference between pre- and post-decannulation highest temperature (p < 0.001) but not maximum white blood cell count (p = 0.66 and p = 0.714) between the two groups. Among all positive culture data, the most commonly isolated organism was Klebsiella pneumoniae (41.7%) followed by Escherichia coli (33%). Median hospital length of stay and time on extracorporeal membrane oxygenation were shorter in the afebrile group compared to the febrile group; however, this did not reach a statistical difference. CONCLUSION: Fever is common in the 48 hours following decannulation from veno-venous extracorporeal membrane oxygenation. Differentiating infection from non-infectious fever in the post-decannulation veno-venous extracorporeal membrane oxygenation population remains challenging. In our febrile post-decannulation cohort, the incidence of healthcare-associated infections was low. The majority were diagnosed with a urinary tract infection. We believe obtaining cultures in febrile patients in the immediate decannulation period from veno-venous extracorporeal membrane oxygenation has utility, and even in the absence of other clinical suspicion, should be considered. However, based on our data, a urinalysis and urine culture may be sufficient as an initial work up to identify the source of infection.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Atención a la Salud , Oxigenación por Membrana Extracorpórea/efectos adversos , Fiebre/etiología , Humanos , Incidencia , Estudios Retrospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA