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BACKGROUND: Survival analysis has been used to characterize the time-to-event data. In medical studies, a typical application is to analyze the survival time of specific cancers by using high-dimensional gene expressions. The main challenges include the involvement of non-informaive gene expressions and possibly nonlinear relationship between survival time and gene expressions. Moreover, due to possibly imprecise data collection or wrong record, measurement error might be ubiquitous in the survival time and its censoring status. Ignoring measurement error effects may incur biased estimator and wrong conclusion. RESULTS: To tackle those challenges and derive a reliable estimation with efficiently computational implementation, we develop the R package AFFECT, which is referred to Accelerated Functional Failure time model with Error-Contaminated survival Times. CONCLUSIONS: This package aims to correct for measurement error effects in survival times and implements a boosting algorithm under corrected data to determine informative gene expressions as well as derive the corresponding nonlinear functions.
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Algoritmos , Humanos , Análisis de Supervivencia , Neoplasias/genética , Neoplasias/mortalidad , Programas Informáticos , Perfilación de la Expresión Génica/métodos , Expresión Génica/genéticaRESUMEN
Importance: Improving end-of-life care in the intensive care unit (ICU) is a priority, but clinically modifiable factors of quality of dying and death (QODD) are seldom identified. Objectives: To comprehensively identify factors associated with QODD classes of dying ICU patients, emphasizing clinically modifiable factors based on the integrative framework of factors associated with for bereavement outcomes. Design, Setting, and Participants: This observational cohort study was conducted at medical ICUs of 2 Taiwanese medical centers from January 2018 to March 2020 with follow-up through December 2022. Eligible participants included primary family surrogates responsible for decision making for critically ill ICU patients at high risk of death (Acute Physiology and Chronic Health Evaluation II score >20) but who survived more than 3 days after ICU admission. Data analysis was conducted from July to September 2023. Main Outcomes and Measures: QODD was measured by the 23-item ICU-QODD questionnaire. Factors associated with patient membership in 4 previously determined QODD classes (high, moderate, poor to uncertain, and worst) were examined using a 3-step approach for latent class modeling with the high QODD class as the reference category. Results: A total of 309 family surrogates (mean [SD] age, 49.83 [12.55] years; 184 women [59.5%] and 125 men [40.5%]) were included in the study. Of all surrogates, 91 (29.4%) were the patients' spouse and 66 (53.7%) were the patients' adult child. Patient demographics were not associated with QODD class. Two family demographics (age and gender), relationship with the patient (spousal or adult-child), and length of ICU stay were associated with QODD classes. Patients of surrogates perceiving greater social support were less likely to be in the poor to uncertain (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94) and worst (aOR, 0.92; 95% CI, 0.87-0.96) QODD classes. Family meetings were associated with the poor to uncertain QODD class (aOR, 8.61; 95% CI, 2.49-29.74) and worst QODD class (aOR, 7.28; 95% CI, 1.37-38.71). Death with cardiopulmonary resuscitation was associated with the worst QODD class (aOR, 7.51; 95% CI, 1.12-50.25). Family presence at patient death was uniformly negatively associated with the moderate QODD class (aOR, 0.16; 95% CI, 0.05-0.54), poor to uncertain QODD class (aOR, 0.21; 95% CI, 0.05-0.82), and worst QODD class (aOR, 0.08; 95% CI, 0.02-0.38). Higher family satisfaction with ICU care was negatively associated with the poor to uncertain QODD class (aOR, 0.93; 95% CI, 0.87-0.98) and worst QODD class (aOR, 0.86; 95% CI, 0.81-0.92). Conclusions and Relevance: In this cohort study of critically ill patients and their family surrogates, modifiable end-of-life ICU-care characteristics played a more significant role in associations with patient QODD class than did immutable family demographics, preexisting family health conditions, patient demographics, and patient clinical characteristics, thereby illuminating actionable opportunities to improve end-of-life ICU care.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Cuidado Terminal , Humanos , Masculino , Femenino , Enfermedad Crítica/mortalidad , Enfermedad Crítica/psicología , Persona de Mediana Edad , Anciano , Cuidado Terminal/psicología , Familia/psicología , Taiwán , Estudios de Cohortes , Encuestas y Cuestionarios , Adulto , AflicciónRESUMEN
PANoptosis is a newly discovered type of cell death characterized by pyroptosis, apoptosis and/or necroptosis and has been implicated in the inflammatory response. Piezo1 is a mechanosensitive ion channel that plays important roles in physiological development and various diseases. However, whether cardiomyocytes undergo PANoptosis during myocardial ischaemia/reperfusion (I/R) injury and the role of Piezo1 in this process remain largely unexplored. In this study, our results revealed that the expression levels of the main components of the PANoptosome, including caspase-8, caspase-3, NLRP3, caspase-1, GSDMD, RIPK1, RIPK3 and MLKL, were significantly upregulated in I/R heart tissues over time, indicating the occurrence of PANoptosis in I/R hearts. Accordingly, Piezo1 expression was significantly upregulated in I/R-injured hearts and hypoxia/reoxygenation (H/R)-treated cardiomyocytes. In contrast, pharmacological inhibition of Piezo1 by the inhibitor GsMTx4 in mice markedly attenuated the I/R-mediated decline in cardiac contractile function and increases in infarct size, apoptosis, oxidative stress and inflammation accompanied by the inhibition of PANoptosis-related mediators in I/R hearts. Consistently, the effects of Piezo1 on calcium influx and PANoptosis were further verified by GsMTx4 and Piezo1 activator Yoda1 in H/R-treated cardiomyocytes in vitro. Moreover, caspase-8 rather than calcium influx was required for H/R-induced PANoptosis in vitro. Mechanistically, Piezo1 interacts with caspase-8, a key initial activator of the PANoptosome complex, which subsequently activates cardiomyocyte PANoptosis, leading to cardiac dysfunction. In summary, these data suggest that Piezo1 is a new cardiac mechanosensor that promotes cardiac I/R injury possibly through the caspase-8-mediated activation of cardiomyocyte PANoptosis and highlight that Piezo1 may represent a new target for treating ischaemic heart disease.
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Caspasa 8 , Canales Iónicos , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Animales , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Caspasa 8/metabolismo , Caspasa 8/genética , Canales Iónicos/metabolismo , Canales Iónicos/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratones , Masculino , Necroptosis , Apoptosis , Oligopéptidos/farmacología , Venenos de Araña , Péptidos y Proteínas de Señalización IntercelularRESUMEN
OBJECTIVES: To examine associations between family surrogates' bereavement outcomes and four previously determined quality of dying and death (QODD) latent classes (high, moderate, poor-to-uncertain, and worst). DESIGN: Prospective, longitudinal, observational study. SETTING: Medical ICUs at two academically affiliated medical centers in Taiwan. PATIENTS/PARTICIPANTS: Three hundred nine family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Health Evaluation II scores > 20) from a disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by the depression and anxiety subscales of the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, 11 items of the Prolonged Grief Disorder (PGD) scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey at 1, 3, 6, 13, 18, and 24 months post-loss. We simultaneously examined associations of four QODD latent classes with physical and mental health-related quality of life (HRQOL) and symptoms of anxiety, depression, post-traumatic stress disorder (PTSD), and PGD assessed over 24 bereavement months using multivariate hierarchical linear modeling. Surrogates' distinct QODD latent classes assessed at 1-month post-loss were significantly associated with bereavement outcomes, except for physical HRQOL and PGD symptoms. Significantly more depressive symptoms and worse mental HRQOL (ß [95% CI]) were reported by bereaved surrogates in the moderate (1.958 [1.144-2.772], -2.245 [-3.961 to -0.529]), poor-to-uncertain (2.224 [1.438-3.010], -7.026 [-8.683 to -5.369]), and worst (2.081 [1.215-2.964], -4.268 [-6.096 to -2.440]) QODD classes than those in the high QODD class. Bereaved surrogates in the moderate (2.095 [1.392-2.798]) and poor-to-uncertain (0.801 [0.123-1.480]) QODD classes reported more anxiety symptoms, whereas those in the poor-to-uncertain QODD class suffered more PTSD symptoms (2.889 [1.005-4.774]) than those in the high QODD class. CONCLUSIONS: The four distinct QODD latent classes were significantly associated with ICU family surrogates' bereavement outcomes, suggesting targets to improve end-of-life care quality in ICUs.
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Ansiedad , Aflicción , Familia , Unidades de Cuidados Intensivos , Calidad de Vida , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Familia/psicología , Calidad de Vida/psicología , Taiwán/epidemiología , Estudios Longitudinales , Anciano , Depresión/epidemiología , Adulto , Enfermedad Crítica/psicología , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/epidemiología , Análisis de Clases LatentesRESUMEN
OBJECTIVE: This cohort study identified patterns/classes of surrogates' assessment of their relative's quality of dying and death (QODD) and to evaluate their associations with family satisfaction with intensive care unit (ICU) care. METHODS: We identified QODD classes through latent class analysis of the frequency component of the QODD questionnaire and examined their differences in summary questions on the QODD and scores of the Family Satisfaction in the ICU questionnaire among 309 bereaved surrogates of ICU decedents. RESULTS: Four distinct classes (prevalence) were identified: high (41.3%), moderate (20.1%), poor-to-uncertain (21.7%) and worst (16.9%) QODD classes. Characteristics differentiate these QODD classes including physical symptom control, emotional preparedness for death, and amount of life-sustaining treatments (LSTs) received. Patients in the high QODD class had optimal physical symptom control, moderate-to-sufficient emotional preparedness for death and few LSTs received. Patients in the moderate QODD class had adequate physical symptom control, moderate-to-sufficient emotional preparedness for death and the least LSTs received. Patients in the poor-to-uncertain QODD class had inadequate physical symptom control, insufficient-uncertain emotional preparedness for death and some LSTs received. Patients in the worst QODD class had poorest physical symptom control, insufficient-to-moderate emotional preparedness for death and substantial LSTs received. Bereaved surrogates in the worst QODD class scored significantly lower in evaluations of the patient's overall QODD, and satisfaction with ICU care and decision-making process than those in the other classes. CONCLUSIONS: The identified distinct QODD classes offer potential actionable direction for improving quality of end-of-life ICU care.
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Cuidado Terminal , Humanos , Estudios de Cohortes , Familia/psicología , Unidades de Cuidados Intensivos , Encuestas y Cuestionarios , Satisfacción PersonalRESUMEN
Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.
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Fibrilación Atrial , Cardiología , Insuficiencia Cardíaca , Hipertensión , Síndromes de la Apnea del Sueño , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Taiwán , Volumen Sistólico , Hipertensión/complicaciones , Hipertensión/diagnóstico , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/terapia , Cuidados Críticos , SueñoRESUMEN
Eu3+ ,Dy3+ co-doped Sr2 LaZrO5.5 -based phosphors were prepared through a sol-gel method. Through characterization, it was found that the Sr2 LaZrO5.5 -based fluorescent powder co-doped with Eu3+ and Dy3+ had a cubic structure. At an excitation wavelength of 290 nm, the substrate Sr2 LaZrO5.5 exhibited strong blue emission at 468 nm, and the Sr2 LaZrO5.5 :18%Eu3+ phosphor exhibited a strong red emission peak at 612 nm. When the doping amount of Dy3+ was 5, 8, 12, 15, or 18%, the Sr2 LaZrO5.5 :18%Eu3+ phosphor changed from an orange-red light, to a warm white light, and to a cold white light. According to the emission spectra, the emission intensities of the substrates Sr2 LaZrO5.5 and Sr2 LaZrO5.5 :Eu3+ decreased with increasing Dy3+ concentration, confirming the energy transfer between the host Sr2 LaZrO5.5 -Eu3+ ,Dy3+ , and resulting in a lower CCT value, with significantly improved white light emission.
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Disprosio , Luminiscencia , Disprosio/química , Luz , Transferencia de Energía , Luz RojaRESUMEN
Necroptosis and apoptosis contribute to the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury and subsequent heart failure. N-arachidonoylphenolamine (AM404) is a paracetamol lipid metabolite that has pleiotropic activity to modulate the endocannabinoid system. However, the protective role of AM404 in modulating I/R-mediated myocardial damage and the underlying mechanism remain largely unknown. A murine I/R model was generated by occlusion of the left anterior descending artery. AM404 (20 mg/kg) was injected intraperitoneally into mice at 2 and 24 h before the I/R operation. Our data revealed that AM404 administration to mice greatly ameliorated I/R-triggered impairment of myocardial performance and reduced infarct area, myocyte apoptosis, oxidative stress and inflammatory response accompanied by the reduction of receptor interacting protein kinase (RIPK)1/3- mixed lineage kinase domain-like (MLKL)-mediated necroptosis and upregulation of the immunosubunits (ß2i and ß5i). In contrast, administration of epoxomicin (a proteasome inhibitor) dramatically abolished AM404-dependent protection against myocardial I/R damage. Mechanistically, AM404 treatment increases ß5i expression, which interacts with Pellino-1 (Peli1), an E3 ligase, to form a complex with RIPK1/3, thereby promoting their degradation, which leads to inhibition of cardiomyocyte necroptosis in the I/R heart. In conclusion, these findings demonstrate that AM404 could prevent cardiac I/R damage and may be a promising drug for the treatment of ischaemic heart disease.
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Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Necroptosis , Apoptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Isquemia , Reperfusión , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Importance: Family surrogates of patients who die in an intensive care unit (ICU) are at risk of cooccurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depressive disorder during bereavement, but symptom trajectories are often explored individually. Objectives: To simultaneously examine and determine co-occurrence of PGD, PTSD, and depressive symptom trajectories. Design, Setting, and Participants: This cohort study was conducted in ICUs of 2 Taiwanese medical centers from January 2018 to March 2020, with follow-up through July 2022. Participants included surrogates responsible for decision-making who provided data 6 to 24 months after the death of their loved one. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGD was assessed with the 11 grief symptom items of the PG-13; PTSD, the Impact of Event Scale-Revised; and depressive symptoms, the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months after the death. Latent growth mixture modeling was conducted to identify distinct trajectories, and joint latent class analysis was used to assess joint patterns of trajectories. Results: A total of 303 participants were included, with most younger than 56 years (207 participants [68.3%]), female (177 participants [58.4%]), and married (228 participants [75.2%]), and their relationship with the patient was mostly spouse (88 participants [29.0%]) or adult child (166 participants [54.8%]). Three trajectories were identified each for PGD, PTSD, and depressive symptoms. A resilience trajectory was predominant across PGD (253 participants [83.5%]), PTSD (250 participants [82.5%]), and depressive (200 participants [66.0%]) symptoms. Second most common was a recovery trajectory identified for PGD (36 participants [11.9%]) and PTSD (41 participants [13.5%]) symptoms, while for depressive symptoms, a moderate trajectory (72 participants [23.8%]) signified persistent moderate distress. A chronic trajectory characterized by persistently high distress was identified for PGD (14 participants [4.6%]) and depressive (31 participants [10.2%]) symptoms, whereas a unique delayed-onset trajectory (12 participants [4.0%]) was identified for PTSD symptoms. Most family surrogates (228 participants [75.2%]) experienced cooccurring PGD, PTSD, and depressive symptom trajectories, but multiple patterns were discordant. Symptom trajectories cooccurred in joint patterns: resilient (247 participants [81.5%]), recovered (43 participants [14.1%]), and distressed (14 participants [4.5%]). These patterns were characterized by high conditional probabilities for the resilience (PGD, 0.999; PTSD, 0.999; depressive, 0.804), recovery (PGD, 0.854; PTSD, 0.890; depressive, 0.588), and chronic (PGD, 0.921; PTSD, 0.789; depressive, 0.980) symptom trajectories. Conclusions and Relevance: In this cohort study, grief-related psychological symptoms evolved in complex ways during ICU bereavement, as characterized by heterogeneous trajectories. Some ICU bereaved surrogates experienced persistent elevated PGD, PTSD, and depressive symptoms individually or conjointly, underscoring the importance of early screening to identify this population at high risk of comorbid psychological distress trajectories.
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Aflicción , Trastornos por Estrés Postraumático , Adulto , Humanos , Femenino , Trastornos por Estrés Postraumático/psicología , Depresión/psicología , Estudios de Cohortes , PesarRESUMEN
The proteasome is the main complex responsible for maintaining intracellular protein homeostasis, impairment of which is associated with cardiac ischaemia/reperfusion (I/R) injury. The small molecule TCH-165 has been found to activate the 20S proteasome to remove disordered proteins in multiple myeloma and glioblastoma. However, the preventive effect of TCH-165 against I/R-mediated cardiac impairment in mice remains largely unknown. Here, a cardiac I/R model was established in mice. Heart function was assessed with echocardiography. Cardiac infarction, myocyte death, and superoxide level were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC)-Evans blue staining, terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL) assay and immunostaining, respectively. Our results showed that TCH-165 treatment markedly ameliorated I/R-mediated cardiac dysfunction and decreased the infarct size, apoptosis, and superoxide levels. Mechanistically, TCH-165 increased immunoproteasome subunit expression/activity, increasing pro-fission protein dynamin-1-like protein (DNM1L, also known as DRP1) degradation and the expression of the pro-fusion proteins mitofusin 1/2 (Mfn1/2) and thereby leading to mitochondrial fission/fusion balance. In vitro experiments confirmed that inhibition of proteasome activity by epoxomicin abolished the protective effect of TCH-165 against hypoxia/reoxygenation (H/R)-induced increases in cardiomyocyte apoptosis, superoxide production and mitochondrial fission. In summary, TCH-165 is a newly discovered inducer of immunoproteasome activity that exerts a preventive effect against cardiac I/R damage by targeting Drp1 degradation, indicating that it may be as a potential therapeutic candidate for ischaemic heart disease.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Isquemia Miocárdica , Animales , Ratones , Complejo de la Endopetidasa Proteasomal , Dinámicas Mitocondriales , Superóxidos , Corazón , Infarto del Miocardio/prevención & controlRESUMEN
In this paper, we analyze the length-biased and partly interval-censored data, whose challenges primarily come from biased sampling and interfere induced by interval censoring. Unlike existing methods that focus on low-dimensional data and assume the covariates to be precisely measured, sometimes researchers may encounter high-dimensional data subject to measurement error, which are ubiquitous in applications and make estimation unreliable. To address those challenges, we explore a valid inference method for handling high-dimensional length-biased and interval-censored survival data with measurement error in covariates under the accelerated failure time model. We primarily employ the SIMEX method to correct for measurement error effects and propose the boosting procedure to do variable selection and estimation. The proposed method is able to handle the case that the dimension of covariates is larger than the sample size and enjoys appealing features that the distributions of the covariates are left unspecified.
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Tamaño de la Muestra , Análisis de Supervivencia , Simulación por ComputadorRESUMEN
Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.
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Apnea Obstructiva del Sueño , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Apnea Obstructiva del Sueño/terapia , Presión de las Vías Aéreas Positiva Contínua , Norepinefrina/uso terapéuticoRESUMEN
Mitochondrial dynamics are critical for maintaining mitochondrial morphology and function during cardiac ischemia and reperfusion (I/R). The immunoproteasome complex is an inducible isoform of the proteasome that plays a key role in modulating inflammation and some cardiovascular diseases, but the importance of immunoproteasome catalytic subunit ß2i (also known as LMP10 or MECL1) in regulating mitochondrial dynamics and cardiac I/R injury is largely unknown. Here, using ß2i-knockout (KO) mice and rAAV9-ß2i-injected mice, we discovered that ß2i expression and its trypsin-like activity were significantly attenuated in the mouse I/R myocardium and in patients with myocardial infarction (MI). Moreover, ß2i-KO mice exhibited greatly enhanced I/R-mediated cardiac dysfunction, infarct size, myocyte apoptosis and oxidative stress accompanied by excessive mitochondrial fission due to Mfn1/2 and Drp1 imbalance. Conversely, cardiac overexpression of ß2i in mice injected with recombinant adeno-associated virus 9 (rAAV9)-ß2i ameliorated cardiac I/R injury. Mechanistically, I/R injury reduced ß2i expression and activity, which increased the expression of the E3 ligase Parkin protein and promoted the degradation of mitofusin 1/2 (Mfn1/2), leading to excessive mitochondrial fission. In conclusion, our data suggest for the first time that ß2i exerts a protective role against cardiac I/R injury and that increasing ß2i expression may be a new therapeutic option for cardiac ischemic disease in clinical practice. Graphical abstract showing how the immunoproteasome subunit ß2i ameliorates myocardial I/R injury by regulating Parkin-Mfn1/2-mediated mitochondrial fusion.
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Daño por Reperfusión Miocárdica , Ratones , Animales , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Dinámicas Mitocondriales/fisiología , Corazón , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Apoptosis , Ratones Noqueados , Hidrolasas/metabolismo , Miocitos Cardíacos/metabolismo , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismoRESUMEN
Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution. Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models. Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1. Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted.
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Calidad de Vida , Apnea Obstructiva del Sueño , Humanos , Niño , Resultado del Tratamiento , Dieta , AzúcaresRESUMEN
BACKGROUND/OBJECTIVE: Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years. METHODS: In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD. RESULTS: Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585-0.770, 0.546-0.780, and 0.440-0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year. CONCLUSIONS: Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.
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Aflicción , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Depresión/psicología , Estudios Prospectivos , Ansiedad , Familia/psicología , Unidades de Cuidados IntensivosRESUMEN
Feature screening is a useful and popular tool to detect informative predictors for ultrahigh-dimensional data before developing statistical analysis or constructing statistical models. While a large body of feature screening procedures has been developed, most methods are restricted to examine either continuous or discrete responses. Moreover, even though many model-free feature screening methods have been proposed, additional assumptions are imposed in those methods to ensure their theoretical results. To address those difficulties and provide simple implementation, in this paper we extend the rank-based coefficient of correlation to develop a feature screening procedure. We show that this new screening criterion is able to deal with continuous and binary responses. Theoretically, the sure screening property is established to justify the proposed method. Simulation studies demonstrate that the predictors with nonlinear and oscillatory trajectories are successfully retained regardless of the distribution of the response. Finally, the proposed method is implemented to analyze two microarray datasets.
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Modelos Estadísticos , Simulación por ComputadorRESUMEN
Oxidative stress is considered a key factor contributing to the initiation and development of cardiac injury following ischaemiaâreperfusion (I/R). Arachidonate 5-lipoxygenase (ALOX5) is a rate-limiting enzyme for leukotriene biosynthesis. MK-886 is an inhibitor of ALOX5 that exhibits anti-inflammatory and antioxidant activities. However, the significance of MK-886 in preventing I/R-mediated cardiac injury and the underlying mechanism remain unclear. Cardiac I/R model was produced by ligation/release of the left anterior descending artery. MK-886 (20 mg/kg) was administered intraperitoneally into mice at 1 and 24 h before I/R. Our results indicated that MK-886 treatment significantly attenuated I/R-mediated cardiac contractile dysfunction and decreased the infarct area, myocyte apoptosis, and oxidative stress accompanied with reduction of Kelch-like ECH-associated protein 1 (keap1) and upregulation of nuclear factor erythroid 2-related factor 2 (NRF2). Conversely, administration of the proteasome inhibitor epoxomicin and NRF2 inhibitor ML385 greatly abrogated MK-886-mediated cardioprotection after I/R injury. Mechanistically, MK-886 enhanced the expression of the immunoproteasome subunit ß5i, which interacted with keap1 and enhanced its degradation, leading to activation of the NRF2-dependent antioxidant response and improvement of mitochondrial fusion-fission balance in the I/R-treated heart. In summary, our present findings indicated that MK-886 could protect the heart against I/R injury and highlight that MK-886 may represent a promising therapeutic candidate for preventing ischaemic disease.
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Antioxidantes , Daño por Reperfusión , Ratones , Animales , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/fisiología , ApoptosisRESUMEN
OBJECTIVES: Grief-related psychological distress often co-occurs to conjointly impair function during bereavement. Knowledge of comorbid grief-related psychological distress is limited: no longitudinal study has examined dynamic patterns of co-occurring prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression, and previous assessment time frames have been variable and potentially inadequate given the duration criterion for PGD. Therefore, the purpose of this study was to investigate the transition of distinct symptom states based on the co-occurrence of PGD, PTSD, and depression symptoms for ICU bereaved surrogates over their first two bereavement years. DESIGN: Prospective, longitudinal, observational study. SETTING: Medical ICUs at two academically affiliated medical centers in Taiwan. PATIENTS/PARTICIPANTS: Three hundred three family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Evaluation II scores > 20) from a disease. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by 11 items of the Prolonged Grief Disorder (PG-13) scale, the Impact of Event Scale-Revised, and the depression subscale of the Hospital Anxiety and Depression Scale at 6, 13, 18, and 24 months postloss. PGD-PTSD-depression-symptom states and their evolution were examined by latent transition analysis. The following four distinct PGD-PTSD-depression-symptom states (prevalence) were initially identified: resilient (62.3%), subthreshold depression-dominant (19.9%), PGD-dominant (12.9%), and PGD-PTSD-depression comorbid (4.9%) states. These PGD-PTSD-depression-symptom states remained highly stable during the first two bereavement years, with transitions predominantly toward resilience. Prevalence for each state at 24 months postloss was 82.1%, 11.4%, 4.0%, and 2.5%, respectively. CONCLUSIONS: Four highly stable PGD-PTSD-depression-symptom states were identified, highlighting the importance of screening for subgroups of ICU bereaved surrogates with increased PGD or comorbid PGD, PTSD, and depression symptoms during early bereavement.
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Aflicción , Depresión , Trastorno de Duelo Prolongado , Trastornos por Estrés Postraumático , Humanos , Depresión/epidemiología , Depresión/psicología , Estudios Prospectivos , Trastornos por Estrés Postraumático/diagnóstico , Estudios LongitudinalesRESUMEN
Background: Obstructive sleep apnea (OSA) is associated with impaired sleep quality and autonomic dysfunction. Adenotonsillectomy significantly improves subjective and objective sleep quality in children with OSA. However, the postoperative changes in heart rate variability (HRV) indices (indicators of cardiac autonomic function) and their importance remain inconclusive in childhood OSA. This retrospective case series aimed to investigate the association of sleep HRV indices, total OSA-18 questionnaire score (a subjective indicator of sleep quality) and polysomnographic parameters (objective indicators of sleep quality), and effects of adenotonsillectomy on HRV indices, total OSA-18 questionnaire score and polysomnographic parameters in children with OSA. Methods: Seventy-six children with OSA were included in baseline analysis, of whom 64 (84%) completed at least 3 months follow-up examinations after adenotonsillectomy and were included in outcome analysis. Associations between baseline variables, and relationships with treatment-related changes were examined. Results: Multivariable linear regression models in the baseline analysis revealed independent relationships between tonsil size and obstructive apnea-hypopnea index (OAHI), adenoidal-nasopharyngeal ratio and very low frequency (VLF) power of HRV (an indicator of sympathetic activity), and normalized low frequency power (an indicator of sympathetic activity) and OAHI. The outcome analysis showed that adenotonsillectomy significantly improved standard deviation of all normal-to-normal intervals, and high frequency power, QoL (in terms of reduced total OSA-18 questionnaire score), OAHI and hypoxemia. Using a conceptual serial multiple mediation model, % change in OSA-18 questionnaire score and % change in VLF power serially mediated the relationships between change in tonsil size and % change in OAHI. Conclusions: The improvement in OAHI after adenotonsillectomy was serially mediated by reductions in total OSA-18 questionnaire score and VLF power. These preliminary findings are novel and provide a direction for future research to investigate the effects of VLF power-guided interventions on childhood OSA.