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1.
J Ultrasound ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806858

ABSTRACT

Congenital portosystemic shunts (CPSS) are a rare developmental anomaly diverting blood flow from the portal venous system and the liver to the systemic venous system. This case series examines the sonographic imaging findings, shunt classification, ultrasound shunt ratios, and outcomes in nine children (5 females, 4 males) admitted to our institution between 2015 and 2022 were included in this study. The shunts were initially categorized by the Parks classification and were followed by serial ultrasounds. Clinical presentation, clinical course, laboratory data, shunt ratios, and time to shunt closure were all followed on subsequent ultrasounds. The most common type of CPPS was the Type 3 shunt. In cases where shunt ratios were measured, the shunt ratio gradually decreased in tandem with decreasing ammonia levels until spontaneous closure was achieved. Predictors of lack of shunt closure included high shunt ratios and Type 4 shunts. Patients with CPPS can be followed with the shunt ratio calculation obtained from sonographic imaging, which may correlate to ammonia levels and indicate risk of hepatic encephalopathy as well as predict speed and timing of closure.

2.
Sci Rep ; 14(1): 4821, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38413800

ABSTRACT

Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4-7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established.


Subject(s)
Lung , Pulmonary Disease, Chronic Obstructive , Humans , Lung/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Mitochondrial Turnover , Mitochondria/metabolism , Epithelial Cells/metabolism , RNA-Binding Proteins/metabolism
3.
Skeletal Radiol ; 53(2): 401-406, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37556017

ABSTRACT

Primary lymphoma of the bone (PLB) is a rare entity, with a majority of pediatric cases presenting in the metaphysis of long bones. There have been only seven reported cases to date of pediatric lymphoma of the bone arising from the epiphysis, of which only two have been described in the proximal tibia. We report a pediatric case of PLB in the tibial epiphysis which presented initially with knee pain. Imaging was performed with X-ray, MRI, CT, and PET-CT with bone biopsies revealing diffuse large B-cell lymphoma. This patient also showed a second, synchronous lesion in the left iliac bone, which was also biopsy proven to diffuse large B-cell lymphoma. Lymphoma in the epiphysis for children is rare and often confused with infectious etiologies or other types of tumors. Misdiagnosis may result in inappropriate treatment and possible progression of the disease, thus making early identification important to initiate therapy.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Humans , Child , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/pathology , Radiography , Epiphyses/diagnostic imaging , Epiphyses/pathology , Magnetic Resonance Imaging
4.
Pediatr Obes ; 18(10): e13066, 2023 10.
Article in English | MEDLINE | ID: mdl-37458161

ABSTRACT

BACKGROUND/OBJECTIVES: Electronic phenotyping is a method of using electronic-health-record (EHR) data to automate identifying a patient/population with a characteristic of interest. This study determines validity of using EHR data of children with overweight/obesity to electronically phenotype evidence of clinician 'attention' to high body mass index (BMI) and each of four distinct comorbidities. METHODS: We built five electronic phenotypes classifying 2-18-year-old children with overweight/obesity (n = 17,397) by electronic/health-record evidence of distinct attention to high body mass index, hypertension, lipid disorders, fatty liver, and prediabetes/diabetes. We reviewed, selected and cross-checked random charts to define items clinicians select in EHRs to build problem lists, and to order medications, laboratory tests and referrals to electronically classify attention to overweight/obesity and each comorbidity. Operating characteristics of each clinician-attention phenotype were determined by comparing comprehensive chart review by reviewers masked to electronic classification who adjudicated evidence of clinician attention to high BMI and each comorbidity. RESULTS: In a random sample of 817 visit-records reviewed/coded, specificity of each electronic phenotype is 99%-100% (with PPVs ranging from 96.8% for prediabetes/diabetes to 100% for dyslipidemia and hypertension). Sensitivities of the attention classifications range from 69% for hypertension (NPV, 98.9%) to 84.7% for high-BMI attention (NPV, 92.3%). CONCLUSIONS: Electronic phenotypes for clinician attention to overweight/obesity and distinct comorbidities are highly specific, with moderate (BMI) to modest (each comorbidity) sensitivity. The high specificity supports using phenotypes to identify children with prior high-BMI/comorbidity attention.


Subject(s)
Diabetes Mellitus , Fatty Liver , Hypertension , Prediabetic State , Humans , Body Mass Index , Overweight , Obesity/diagnosis , Obesity/epidemiology , Hypertension/diagnosis , Hypertension/epidemiology , Electronic Health Records , Phenotype , Primary Health Care , Lipids
5.
Cells ; 12(2)2023 01 12.
Article in English | MEDLINE | ID: mdl-36672235

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease for which cigarette smoking is the main risk factor. Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known to be formed during pyrolysis and combustion of tobacco and have been linked to respiratory toxicity. Mitochondrial dysfunction is suggested to be mechanistically and causally involved in the pathogenesis of smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has been shown to impair the molecular regulation of mitochondrial metabolism and content in epithelial cells of the airways and lungs. Although it is unknown which specific chemicals present in CS are responsible for this, it has been suggested that aldehydes may be involved. Therefore, it has been proposed by the World Health Organization to regulate aldehydes in commercially-available cigarettes. In this review, we comprehensively describe and discuss the impact of acetaldehyde, acrolein, and formaldehyde on mitochondrial function and content and the molecular pathways controlling this (biogenesis versus mitophagy) in epithelial cells of the airways and lungs. In addition, potential therapeutic applications targeting (aldehyde-induced) mitochondrial dysfunction, as well as regulatory implications, and the necessary required future studies to provide scientific support for this regulation, have been covered in this review.


Subject(s)
Cigarette Smoking , Pulmonary Disease, Chronic Obstructive , Nicotiana/adverse effects , Aldehydes/metabolism , Acrolein/toxicity , Acrolein/metabolism , Cigarette Smoking/adverse effects , Lung/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Epithelial Cells/metabolism , Formaldehyde , Acetaldehyde/toxicity , Acetaldehyde/metabolism , Mitochondria/metabolism
6.
Pediatr Radiol ; 53(1): 112-120, 2023 01.
Article in English | MEDLINE | ID: mdl-35879446

ABSTRACT

BACKGROUND: While neonatal brain US is emerging as an imaging modality with greater portability, widespread availability and relative lower cost compared to MRI, it is unknown whether US is being maximized in infants to increase sensitivity in detecting intracranial pathology related to common indications such as hemorrhage, ischemia and ventriculomegaly. OBJECTIVE: To survey active members of the Society for Pediatric Radiology (SPR) regarding their utilization of various cranial US techniques and reporting practices in neonates. MATERIALS AND METHODS: We distributed an online 10-question survey to SPR members to assess practice patterns of neonatal cranial US including protocol details, use of additional sonographic views, perceived utility of spectral Doppler evaluation, and germinal matrix hemorrhage and ventricular size reporting preferences. RESULTS: Of the 107 institutions represented, 90% of respondents were split evenly between free-standing children's hospitals and pediatric departments attached to a general hospital. We found that most used template reporting (72/107, 67%). The anterior fontanelle approach was standard practice (107/107, 100%). We found that posterior fontanelle views (72% sometimes, rarely or never) and high-frequency linear probes to evaluate far-field structures (52% sometimes, rarely or never) were seldom used. Results revealed a range of ways to report germinal matrix hemorrhage and measure ventricular indices to assess ventricular dilatation. There was substantial intra-institutional protocol and reporting variability as well. CONCLUSION: Our results demonstrate high variability in neurosonography practice and reporting among active SPR members, aside from the anterior fontanelle views, template reporting and linear high-resolution near-field evaluation. Standardization of reporting germinal matrix hemorrhage and ventricular size would help ensure a more consistent application of neonatal US in research and clinical practice.


Subject(s)
Hydrocephalus , Radiology , Infant , Infant, Newborn , Child , Humans , Brain , Surveys and Questionnaires , Magnetic Resonance Imaging/methods , Cerebral Hemorrhage
7.
Cells ; 11(21)2022 11 03.
Article in English | MEDLINE | ID: mdl-36359877

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease primarily caused by exposure to cigarette smoke (CS). During the pyrolysis and combustion of tobacco, reactive aldehydes such as acetaldehyde, acrolein, and formaldehyde are formed, which are known to be involved in respiratory toxicity. Although CS-induced mitochondrial dysfunction has been implicated in the pathophysiology of COPD, the role of aldehydes therein is incompletely understood. To investigate this, we used a physiologically relevant in vitro exposure model of differentiated human primary bronchial epithelial cells (PBEC) exposed to CS (one cigarette) or a mixture of acetaldehyde, acrolein, and formaldehyde (at relevant concentrations of one cigarette) or air, in a continuous flow system using a puff-like exposure protocol. Exposure of PBEC to CS resulted in elevated IL-8 cytokine and mRNA levels, increased abundance of constituents associated with autophagy, decreased protein levels of molecules associated with the mitophagy machinery, and alterations in the abundance of regulators of mitochondrial biogenesis. Furthermore, decreased transcript levels of basal epithelial cell marker KRT5 were reported after CS exposure. Only parts of these changes were replicated in PBEC upon exposure to a combination of acetaldehyde, acrolein, and formaldehyde. More specifically, aldehydes decreased MAP1LC3A mRNA (autophagy) and BNIP3 protein (mitophagy) and increased ESRRA protein (mitochondrial biogenesis). These data suggest that other compounds in addition to aldehydes in CS contribute to CS-induced dysregulation of constituents controlling mitochondrial content and function in airway epithelial cells.


Subject(s)
Aldehydes , Pulmonary Disease, Chronic Obstructive , Humans , Aldehydes/metabolism , Acrolein/toxicity , Acrolein/metabolism , Epithelial Cells/metabolism , Mitochondria/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Acetaldehyde/toxicity , Acetaldehyde/metabolism , Nicotiana , Formaldehyde , RNA, Messenger/metabolism , Smoking
8.
J Am Board Fam Med ; 35(4): 742-750, 2022.
Article in English | MEDLINE | ID: mdl-35896456

ABSTRACT

BACKGROUND: Primary-care providers, clinic staff, and nurses play an important role in reducing child obesity; yet time restraints and clinical demands compete with effective pediatric weight management and prevention. METHODS: To investigate the potential impact of an electronic health record (EHR) enabled tool to assist primary care teams in addressing child obesity, we conducted a controlled effectiveness study of FitTastic compared with usual care on the BMI pattern of 291 children (2 to 17 years) up to 4 years later. RESULTS: Per χ2 analysis, a greater proportion of children with baseline overweight/obesity in the EHR tool group than the control group had a favorable BMI pattern (32% vs 13%, P = .03). In logistic regression, FitTastic children were more likely than control children to have a favorable BMI pattern at follow-up (OR 3.8, 95% CI 1.1 to 13.2), adjusted for age, gender, race, and parental education. CONCLUSION: Study findings suggest that EHR-enabled tools to assist primary care teams in managing child obesity may be useful for helping to address the weight in children with overweight/obesity, especially in younger children (2 to 5 years). Digital and EHR-enabled technologies may prove useful for partnering health care teams and families in the important tasks of setting positive, family-centered healthy lifestyle behavioral goals and managing child overweight and obesity.


Subject(s)
Pediatric Obesity , Body Mass Index , Child , Electronic Health Records , Healthy Lifestyle , Humans , Overweight/prevention & control , Parents , Pediatric Obesity/prevention & control
9.
Cells ; 11(11)2022 05 28.
Article in English | MEDLINE | ID: mdl-35681466

ABSTRACT

Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp.


Subject(s)
Cigarette Smoking , Streptococcus pneumoniae , Bronchi/metabolism , Epithelial Cells/metabolism , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Streptococcus pneumoniae/metabolism , Nicotiana/adverse effects , Nicotiana/metabolism
10.
Dis Model Mech ; 15(3)2022 03 01.
Article in English | MEDLINE | ID: mdl-35344036

ABSTRACT

Exposure to cigarette smoke (CS) is the primary risk factor for developing chronic obstructive pulmonary disease. The impact of CS exposure on the molecular mechanisms involved in mitochondrial quality control in airway epithelial cells is incompletely understood. Undifferentiated or differentiated primary bronchial epithelial cells were acutely/chronically exposed to whole CS (WCS) or CS extract (CSE) in submerged or air-liquid interface conditions. Abundance of key regulators controlling mitochondrial biogenesis, mitophagy and mitochondrial dynamics was assessed. Acute exposure to WCS or CSE increased the abundance of components of autophagy and receptor-mediated mitophagy in all models. Although mitochondrial content and dynamics appeared to be unaltered in response to CS, changes in both the molecular control of mitochondrial biogenesis and a shift toward an increased glycolytic metabolism were observed in particular in differentiated cultures. These alterations persisted, at least in part, after chronic exposure to WCS during differentiation and upon subsequent discontinuation of WCS exposure. In conclusion, smoke exposure alters the regulation of mitochondrial metabolism in airway epithelial cells, but observed alterations may differ between various culture models used. This article has an associated First Person interview with the joint first authors of the paper.


Subject(s)
Cigarette Smoking , Pulmonary Disease, Chronic Obstructive , Bronchi , Epithelial Cells , Humans , Mitochondria , Mitophagy , Pulmonary Disease, Chronic Obstructive/etiology , Nicotiana/adverse effects
11.
Pediatr Radiol ; 52(3): 429-444, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34505950

ABSTRACT

A palpable finding along the chest wall is a frequent indication for pediatric US. Accurate identification of benign lesions can reassure families and appropriately triage children who need follow-up, cross-sectional imaging, or biopsy. In this pictorial essay, we review chest wall anatomy, illustrate US techniques and discuss key US imaging features of common benign lesions and normal variants.


Subject(s)
Thoracic Wall , Biopsy , Child , Humans , Thoracic Wall/diagnostic imaging , Ultrasonography/methods
12.
Clin Imaging ; 82: 103-109, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34801840

ABSTRACT

Recent literature has raised concerns about the sensitivity and accuracy of radiographs at diagnosing rib fractures. Studies have shown that chest computed tomography (CT) has far greater sensitivity at detecting rib fractures than radiographs. The purpose of this study was to evaluate the sensitivity of skeletal survey (SS) radiographs at diagnosis of rib fractures compared to CT in the pediatric population. This retrospective review included 57 patients who had undergone both a SS and a CT chest or CT chest/abdomen/pelvis within 30 days of each other for the indication of either non-accidental (NAT) or accidental trauma between 2009 and 2017. Images and reports were analyzed by a pediatric radiology fellow for presence/absence of fracture, evidence of healing and location of rib fracture, including rib level, location within the rib (anterior, lateral, and posterior), and side (right versus left). 225 rib fractures were identified in 25 patients on CT. 38 of those fractures were missed on the preceding SS, yielding a miss rate of 17%. Acute fractures were more likely to be missed than chronic or healing fractures (p ≤ 0.01). Location within the rib did not impact rib detection on radiographs. Left-sided rib fractures were not more common in NAT patients, compared to accidental trauma. SS miss approximately 17% of all rib fractures and CT is more sensitive modality in the detection of rib fractures, particularly acute rib fractures, regardless of location. Low-dose Chest CT could be a helpful modality in the work-up of NAT trauma.


Subject(s)
Child Abuse , Rib Fractures , Child , Humans , Radiography , Retrospective Studies , Rib Fractures/diagnostic imaging , Rib Fractures/epidemiology , Tomography, X-Ray Computed
13.
J Hypertens ; 39(9): 1893-1900, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33967240

ABSTRACT

OBJECTIVE: To determine and evaluate the accuracy of methods physicians use to detect diagnostic criteria for pediatric hypertension [hypertensive blood pressures (BPs) on three or more occasions] in electronic health records (EHRs). METHODS: Methods used by pediatric-trained physicians (n = 12) to detect diagnostic criteria for hypertension in a simulation using a child's EHR data were directly observed, timed, and evaluated for accuracy. All physicians were given the same information regarding diagnostic criteria to eliminate knowledge gaps. Then, computer modeling and EHR data from 41 654 3-18-year-olds were used to simulate and compare the accuracy of detecting hypertension criteria using an observed-shorthand method vs. the guideline-recommended/gold-standard method. RESULTS: No physician used the guideline-recommended method of determining multiple time-of-care hypertension thresholds for child age/height at the time of each BP measure. One physician estimated the child's BP diagnosis without computing thresholds; 11 of 12 physicians determined the child's hypertension threshold from age/height data at the time of a current visit and applied/imputed this threshold to BP measured at all visits (current-visit threshold used to assess historical-visit BPs) to detect three separate BP elevations. Physicians took 2.3 min (95% confidence interval, 1.5-3.0) to declare a diagnosis. Sensitivity was 83.1% when applying the current-visit threshold to detect the guideline-recommended-BP-threshold diagnosis using EHR data. Specificity and positive-predictive/negative-predictive values ranged from 98.5 to 99.9%. CONCLUSION: Physicians applied a shorthand method to evaluate pediatric BPs. Computer-simulated comparison of the shorthand and guideline methods using clinical data suggest the shorthand method could yield an inaccurate impression of a child's BP history in 17% of pediatric ambulatory visits.


Subject(s)
Hypertension , Physicians , Child , Electronic Health Records , Humans , Hypertension/diagnosis , Predictive Value of Tests
14.
J Pediatr ; 235: 130-137, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33812920

ABSTRACT

OBJECTIVE: To assess prevalence of and factors associated with left ventricular diastolic dysfunction (LVDD) in youth with obesity and elevated blood pressure (BP). STUDY DESIGN: This was a cross-sectional analysis of baseline and follow-up visits of 83 youth, 5-21 years, evaluated for overweight/obesity and elevated BP in a multidisciplinary clinic. LVDD was defined according to established adult criteria (LVDDadult; E/A < 1, E/e' > 14, or e'/a' < 0.8) and pediatric criteria (LVDDpeds; E/A <10th percentile, E/e' >99th percentile, or e'/a' <1st percentile) based on data from 103 age-sex matched healthy controls. Baseline factors associated with LVDDpeds were examined using Wilcoxon rank sum and χ2 tests. Multiple logistic regression analyses using generalized estimating equations to account for repeated measures evaluated the associations of adiposity and BP with LVDDpeds. RESULTS: The prevalence of LVDD ranged from 1.2% to 2.7% when we used adult criteria and 19% to 28% when we used pediatric criteria. Those with LVDDpeds were older, predominantly male, and non-African American and had greater weight, BP, BP medication use, and non-high-density lipoprotein cholesterol than those without LVDDpeds. Diastolic BP z score was associated with LVDDpeds by E/A (OR 1.95, 95% CI 1.15-3.32, P = .014) after we adjusted for age, sex, race, BP medications, and body mass index z score. CONCLUSIONS: LVDD was present in a substantial proportion of youth with overweight/obesity and elevated BP using pediatric criteria. Those with LVDDpeds had significantly greater measures of adiposity and BP compared with those without LVDDpeds, and diastolic BP z score was an independent predictor of LVDDpeds by E/A. These data emphasize the importance of prevention and treatment of cardiovascular disease risk factors in childhood.


Subject(s)
Diastole , Hypertension/epidemiology , Pediatric Obesity/epidemiology , Ventricular Dysfunction, Left/epidemiology , Adolescent , Age Distribution , Child , Child, Preschool , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Lipoproteins, HDL/analysis , Male , Sex Distribution , Young Adult
15.
Reprod Sci ; 28(8): 2186-2199, 2021 08.
Article in English | MEDLINE | ID: mdl-33523425

ABSTRACT

Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis. Graphical Abstract.


Subject(s)
Mitochondria/metabolism , Oxidative Stress/physiology , Placenta/metabolism , Pre-Eclampsia/metabolism , Adult , Antioxidants/metabolism , Apoptosis/physiology , Female , Humans , Inflammation/metabolism , Pregnancy , Superoxide Dismutase/metabolism , Trophoblasts/metabolism
16.
PLoS One ; 16(1): e0245155, 2021.
Article in English | MEDLINE | ID: mdl-33434211

ABSTRACT

INTRODUCTION: Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown. METHODS: We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia. Furthermore, we explored the therapeutic potential of the antioxidants MitoQ and quercetin in preventing hypoxia-induced placental oxidative stress. RESULTS: Both in placental explants as well as BeWo cells, hypoxia resulted in reductions in mitochondrial content, decreased abundance of key molecules involved in the electron transport chain and increased expression and activity of glycolytic enzymes. Furthermore, expression levels of key regulators of mitochondrial biogenesis were decreased while the abundance of constituents of the mitophagy, autophagy and mitochondrial fission machinery was increased in response to hypoxia. In addition, placental hypoxia was associated with increased oxidative stress, inflammation, and apoptosis. Moreover, experiments with MitoQ revealed that hypoxia-induced reactive oxygen species originated from the mitochondria in the trophoblasts. DISCUSSION: This study is the first to demonstrate that placental hypoxia is associated with mitochondrial-generated reactive oxygen species and significant alterations in the molecular pathways controlling mitochondrial content and function. Furthermore, our data indicate that targeting mitochondrial oxidative stress may have therapeutic benefit in the management of pathologies related to placental hypoxia.


Subject(s)
Mitochondria/metabolism , Organelle Biogenesis , Oxidative Stress , Pre-Eclampsia/metabolism , Reactive Oxygen Species/metabolism , Trophoblasts/metabolism , Cell Hypoxia , Cell Line , Female , Humans , Mitochondria/pathology , Pre-Eclampsia/pathology , Pregnancy , Trophoblasts/pathology
17.
Curr Hypertens Rep ; 22(9): 67, 2020 08 27.
Article in English | MEDLINE | ID: mdl-32852616

ABSTRACT

PURPOSE OF REVIEW: To review literature from 2016 to 2019 on clinical decision support (CDS) for diagnosis and management of hypertension in children and adults. RECENT FINDINGS: Ten studies described hypertension CDS systems. Novel advances included the integration of patient-collected blood pressure data, automated information retrieval and management support, and use of CDS in low-resource/developing-world settings and in pediatrics. Findings suggest that CDS increases hypertension detection/control, yet many children and adults with hypertension remain undetected or undercontrolled. CDS challenges included poor usability (from lack of health record integration, excessive data entry requests, and wireless connectivity challenges) and lack of clinician trust in blood pressure measures. Hypertension CDS has improved but not closed gaps in the detection and control of hypertension in children and adults. The studies reviewed indicate that the usability of CDS and the system where CDS is deployed (e.g., commitment to high-quality blood pressure measurement/infrastructure) may impact CDS's ability to increase hypertension detection and control.


Subject(s)
Decision Support Systems, Clinical , Hypertension , Pediatrics , Adult , Blood Pressure , Blood Pressure Determination , Child , Humans , Hypertension/diagnosis , Hypertension/drug therapy
18.
Skeletal Radiol ; 49(4): 521-530, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31792557

ABSTRACT

Pediatric ankle injuries require timely diagnosis due to their involvement of the distal tibial physis and subsequent impact on long bone growth. These injuries occur in a predictable pattern based on ankle position, direction of force, and degree of closure of the distal tibial physis. The Dias-Tachdjian classification describes possible ankle injury patterns for the completely open physis, and we present a simplified algorithm for applying this system in routine radiographic interpretation. Similar to the Lauge-Hansen classification in adults, the Dias-Tachdjian system is based on the position of the foot and direction of force at the time of injury with four major patterns: supination-inversion, pronation-eversion external rotation, supination-plantar flexion, and supination-external rotation. In addition, we examine the effect that the closing distal tibial physis has on adolescent fracture patterns (specifically, Tillaux and triplane fractures). Awareness of these injury patterns helps the radiologist to identify nondisplaced fractures and subtle physeal injuries with implications for surgical and/or conservative management.


Subject(s)
Ankle Injuries/classification , Ankle Injuries/diagnostic imaging , Radiography/methods , Adolescent , Ankle Joint/diagnostic imaging , Child , Growth Plate/diagnostic imaging , Humans , Supination
19.
Acad Pediatr ; 20(6): 776-783, 2020 08.
Article in English | MEDLINE | ID: mdl-31783183

ABSTRACT

OBJECTIVE: Despite recognition that hypertension is associated with childhood obesity, data suggest that high blood pressure (BP) is infrequently diagnosed in children. This study sought to examine provider communication with overweight school-age children regarding BP measurements that were high at well-child visits. METHODS: Cross-sectional mixed-methods analysis of audio-recorded communication from well-child visits with overweight 6-12-year-olds. Data from the subset of children with elevated BPs were used for this study. Three BP measures obtained at the audio-recorded visit were averaged, paired with historical BPs stored in the health record, and compared to contemporary/Fourth-Report thresholds to determine if children had elevated/hypertensive BPs only at the audio-recorded visit or met hypertension-diagnostic criteria (hypertension-level BP ≥3 separate visits). Two reviewers used visit transcripts to categorize communication about BP as "absent," "unclear," or "direct." Provider use of a billing diagnosis for elevated BP/hypertension in visits with direct-BP-communication was explored. RESULTS: In 36 of 126 (29%) visit-audio-recordings, children had elevated/hypertensive BPs. Thirty-three of the 36 eligible (92%) had intelligible audio-recordings. Of these, 9 (25%) were overweight and 24 (75%) had obesity. Seventeen (52%) had elevated BPs, and 16 (48%) hypertensive BPs. Ten (30%) met criteria for hypertension diagnosis. BP communication was absent in 20 visits (61%), unclear in 8 (24%), and direct in 5 visits (15%). Billing diagnoses for elevated BP/hypertension were entered at 4 of 5 (80%) visits with direct-BP communication. CONCLUSIONS: Most overweight children with elevated BPs did not receive communication that BP is high at well-child visits. Relevant billing diagnoses may indicate direct-BP communication.


Subject(s)
Hypertension/epidemiology , Hypertension/psychology , Overweight/epidemiology , Overweight/psychology , Physician-Patient Relations , Child , Child Health Services , Communication , Cross-Sectional Studies , Female , Humans , Male , Pediatric Obesity/epidemiology , Pediatricians , Pilot Projects , Tape Recording
20.
Am J Prev Med ; 57(3): 384-393, 2019 09.
Article in English | MEDLINE | ID: mdl-31377089

ABSTRACT

INTRODUCTION: This study uses clinical practice data to determine whether recommended weight management clinician behaviors are associated with weight status improvement in children aged 6-12 years who are overweight or obese. METHODS: Electronic health record data (2009-2014) from 52 clinics were used. Weight status was examined from 1 visit to the next as dichotomous improvement (versus worsening or no change) and change in percentage overweight (over sex/age-specific BMI95). The primary predictor was a clinician behavior variable denoting attention to high BMI alone or with assessment of medical risk/comorbidities and was defined using combinations of diagnostic codes and electronic health record orders. Covariates included time between visits and medications associated with weight gain or loss. Adjusted multilevel regression models examined the association of the clinician behavior variable with weight status improvement. Analyses were conducted from 2015 to 2018. RESULTS: Children (n=7,205) had a mean age of 8.9 years; 45.5% were overweight, 54.5% obese, and 81.1% publicly insured. For 62% of overweight children, and 38%, 21%, and 11% of those in obesity classes 1-3, respectively, no attention to high BMI/medical risk assessment at any visit was identified. Children with evidence of clinician attention to high BMI alone and who underwent a medical risk assessment had significantly greater AOR of improvement in percentage of BMI95 and percentage of BMI95 change: BMI alone, AOR=1.2 (p<0.001) and ß= -0.3 (p>0.05); BMI/medical risk, AOR=1.2 and ß= -0.5 (both p<0.001). Other factors associated with weight status improvement included prescription medications (1 or more prescriptions associated with either weight loss or none associated with weight gain) and fewer months between visits. CONCLUSIONS: This is the first study to use electronic health record data to demonstrate that widely recommended clinician behaviors are associated with weight status improvement in children aged 6-12 years who are overweight or obese.


Subject(s)
Clinical Competence , Overweight/prevention & control , Pediatric Obesity/prevention & control , Pediatricians/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Body Mass Index , Body Weight , Child , Child, Preschool , Electronic Health Records/statistics & numerical data , Female , Humans , Male , Overweight/epidemiology , Pediatric Obesity/epidemiology , Pediatricians/psychology , Retrospective Studies , Texas/epidemiology , Weight Gain , Weight Loss
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