Up to an Hour of Donor Resuscitation Does Not Affect Pediatric Heart Transplantation Survival.

BACKGROUND: In pediatric heart transplantation, surgeons historically avoided donors requiring cardiopulmonary resuscitation (CPR), despite evidence that donor CPR does not change posttransplant survival (PTS). This study sought to determine whether CPR duration affects PTS. METHODS: All potential brain-dead donors aged <40 years from 2001 to 2021 consented for heart procurement were identified in the United Network for Organ Sharing database (n = 54,671). Organ acceptance was compared by CPR administration and duration. All recipients aged <18 years with donor CPR data were then identified (n = 5680). Survival analyses were conducted using increasing CPR duration as a cut point to identify the shortest duration beyond which PTS worsened. Additional analyses were performed with multivariable and cubic spline regression. RESULTS: Fifty-one percent of donors (28,012 of 54,671) received CPR. Donor acceptance was lower after CPR (54% vs 66%; P < .001) and across successive quartiles of CPR duration (P < .001). Of the transplant recipients, 48% (2753 of 5680) belonged to the no-CPR group, and 52% (2927 of 5680) belonged to the CPR group. Kaplan-Meier analyses of CPR duration attained significance at 55 minutes, after which PTS worsened (11.1 years vs 9.2 years; P = .025). There was no survival difference between the CPR ≤55 minutes group and the no-CPR group (11.1 years vs 11.2 years; P = .571). A cubic spline regression model confirmed that PTS worsened at more than 55 minutes of CPR. A Cox regression demonstrated that CPR >55 minutes predicted worsened PTS relative to no CPR (HR, 1.51; P = .007) but CPR ≤55 minutes did not (HR, 1.01; P = .864). CONCLUSIONS: Donor CPR decreases organ acceptance for transplantation; however, shorter durations (≤55 minutes) had equivalent PTS when controlling for other risk factors.

Polysomnographic parameters and clinical risk factors predicting postoperative respiratory complications in children undergoing supraglottoplasty.

STUDY OBJECTIVES: Postoperative respiratory complications (PORCs) can occur following supraglottoplasty (SGP) for obstructive sleep apnea. However, there are very limited data on risk factors associated with these complications. This study aims to evaluate the occurrence of PORC in children undergoing SGP and to assess clinical factors and polysomnographic parameters predicting these complications. METHODS: A retrospective study was performed in children with laryngomalacia who underwent SGP with preoperative polysomnography. RESULTS: 400 children who underwent SGP met the criteria for entry into the analysis with a total of 416 surgeries with corresponding preoperative polysomnography. The median age (interquartile range) at the time of polysomnography was 0.4 (0.2, 1.5) years. A total of 96 (23.1%) PORCs were noted. Compared with those without complications, children with PORCs had a higher proportion of congenital heart disease (P < .05), higher median obstructive apnea-hypopnea index (obstructive AHI; median 16.0 vs 11.4 events/h; P < .01), and lower median oxygen saturation (SpO2) (P < .001). The unadjusted odd ratio indicated an increased risk of PORCs in children with congenital heart disease (odds ratio 1.66; P < .05) and those with an obstructive AHI > 10 events/h (odds ratio 2.06; P < .01). Multiple regression analysis demonstrated that an obstructive AHI > 10 events/h was the only independent risk factor for PORCs (P < .05). CONCLUSIONS: In our cohort of children with laryngomalacia undergoing SGP, those with underlying congenital heart disease, higher obstructive AHI, and lower SpO2 were more likely to develop PORCs. Only children with an obstructive AHI > 10 events/h were at significantly increased risk for PORCs following SGP. Preoperative polysomnography is useful in preoperative planning in children undergoing SGP. CITATION: Kanavitoon S, Ngamprasertwong P, Gurbani N, et al. Polysomnographic parameters and clinical risk factors predicting postoperative respiratory complications in children undergoing supraglottoplasty. J Clin Sleep Med. 2024;20(1):9-16.

A Systems Biology Approach for Investigating Significant Biomarkers and Drug Targets Common Among Patients with Gonorrhea, Chlamydia, and Prostate Cancer: A Pilot Study.

Having a previous history of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia increases the chance of developing prostate cancer, the second most frequent malignant cancer among men. However, the molecular functions that cause the development of prostate cancer in persons with gonorrhea and chlamydia are yet unknown. In this study, we studied RNA-seq gene expression profiles using computational biology methods to find out potential biomarkers that could help us in understanding the patho-biological mechanisms of gonorrhea, chlamydia, and prostate cancer. Using statistical methods on the Gene Expression Omnibus (GEO) data sets, it was found that a total of 22 distinct differentially expressed genes were shared among these 3 diseases of which 14 were up-regulated (PGRMC1, TSC22D1, SH3BGRL, NNT, CTSC, FRMD3, CCR2, FAM210B, VCL, PTGS1, SLFN11, SLC40A1, PROS1, and DSE) and the remaining 8 genes were down-regulated (PRNP, HINT3, MARCKSL1, TMED10, SH3KBP1, ENSA, DERL1, and KMT2B). Investigation on these 22 unique dysregulated genes using Gene Ontology, BioCarta, KEGG, and Reactome revealed multiple altered molecular pathways, including regulation of amyloid precursor protein catabolic process, ferroptosis, effects on gene expression of Homo sapiens PPAR pathway, and innate immune system R-HSA-168249. Four significant hub proteins namely VCL, SH3KBP1, PRNP, and PGRMC1 were revealed by protein-protein interaction network analysis. By analyzing gene-transcription factors and gene-miRNAs interactions, significant transcription factors (POU2F2, POU2F1, GATA6, and HIVEP1) and posttranscriptional regulator microRNAs (hsa-miR-7-5p) were also identified. Three potential therapeutic compounds namely INCB3284, CCX915, and MLN-1202 were found to interact with up-regulated protein C-C chemokine receptor type 2 (CCR2) in protein-drug interaction analysis. The proposed biomarkers and therapeutic potential molecules could be investigated for potential pharmacological targets and activity in the fight against in patients with gonorrhea, chlamydia, and prostate cancer.

Nigella sativa Oil Improves Motor Skill Learning of Albino Mice: In Vivo and In Silico Investigations.

Experimental evidences demonstrated that Nigella sativa oil (NSO) can restore neuronal integrities and processes by increasing the neuronal density, decreasing apoptosis, preventing inflammatory processes, and improving the neurogenic cells in the hippocampus. This refurbishment enhances the learning process and memory. The antioxidant defense mechanism of NSO slows down the process of neurodegeneration and motor deficit. The present study aimed to investigate the effects of NSO on motor skill learning using the single pellet reaching task method on Swiss albino mice, followed by in silico studies. Mice (total of 16) were randomly divided into the control group and treatment group (n = 8). The treatment group received 1 ml/kg b.w. NSO orally once daily for 7 days, and a control group received 1 ml/kg normal saline instead of NSO in a similar manner. The average success rate due to ingestion of NSO in the treatment group mice increased significantly (P < 0.05) compared to controlled mice. Molecular docking analysis revealed that thymoquinone, carvacrol, thymohydroquinone, p-cymene, and t-anethole have binding affinities for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) that ranges from (-5.1 to -6.2) kcal/mol, which is comparable to the reference ligand glutamic acid binding affinity with AMPA-R (-6.6 kcal/mol). Thymoquinone and carvacrol formed hydrogen bonds with AMPA receptor at TYR61, SER142, and SER143 residues, comparable to the binding affinity of glutamic acid. ADMET analysis reported that all the compounds have higher bioavailability (>90%) and can cross the BBB easily (logBB> 0.3). Based on our experimental data and in silico report, we concluded that the enhanced motor skill learning effects of NSO are due to presence of potent antioxidants-thymoquinone and carvacrol-which might serve as AMPA receptor agonists. These phytoconstituents may play role in synaptic strengthening and promote experience-dependent motor skill learning.

Longitudinal mental health trends in cystic fibrosis.

BACKGROUND: Mental health screening in accordance with consensus guidelines became routine clinical practice in our cystic fibrosis (CF) Center in 2015. We hypothesized improvement in anxiety and depression symptoms over time and associations between elevated screening scores and disease severity. We aimed to observe the impact of the COVID-19 pandemic and modulator use on mental health symptoms. METHODS: Retrospective chart reviews were conducted for people 12 years and older with at least one Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9) screening for six years. Descriptive statistics were used to summarize demographic variables and logistic regression and linear mixed models were used to evaluate the relationship between screening scores and clinical variables. RESULTS: Analyses included 150 participants (ages 12-22 years). The percentage of minimal to no symptom scores increased over time for anxiety and depression. Increased mental health visits and CFRD were associated with higher PHQ-9 and GAD-7 scores. Higher FEV1pp was associated with lower GAD-7 and PHQ-9 scores. More effective modulator use was associated with lower PHQ-9 scores. Mean PHQ-9 and GAD-7 scores were not significantly different when comparing pre-pandemic and pandemic scores. CONCLUSION: Disruptions in screening during the pandemic were minimal and symptom scores remained stable. Individuals with higher mental health screening scores were more likely to have CFRD and utilization of mental health services. Consistent mental health monitoring and support is needed so individuals with CF can endure anticipated and unanticipated stressors including changes in physical health, healthcare, and societal stressors such as COVID-19 pandemic.

Body mass index percentage and survival in pediatric patients listed for lung transplantation: A modern-era multi-institutional analysis.

BACKGROUND: Prior studies suggest that being underweight by body mass index percentiles (BMI%) or thinness grade did not affect post-transplant survival in pediatric lung transplant (LTx) recipients regardless of cystic fibrosis (CF) or non-CF diagnosis. Graft and overall survival from the time of listing was instead evaluated based on listing BMI%, the current standard of practice for BMI definitions in pediatrics, to ascertain the impact of a "severely low" subcategory. METHODS: The UNOS registry was queried for children listed for LTx (aged 2 to <18 years) from January 1986 to March 2020. BMI% at listing and transplant were calculated per CDC guidelines according to age in years, sex, and reported BMI%. Patients were divided by listing BMI%: severely low (<3rd), low (3-<5th), normal (5-<85th), overweight (85-<95th), and obese (≥95th). Kaplan-Meier curves were generated to assess differences in overall survival since listing based on BMI% classes. Cox proportional-hazards models were developed to assess risk factors for overall and graft survival, including listing BMI%, transplant listing era (≥2005), and listing age, by reporting hazard ratios (HR). RESULTS: Listing BMI% was calculable for 1,876 patients. The proportion of patients with CF differed significantly between BMI% groups (p < 0.001). Patients listed with a non-CF diagnosis comprised 34% of those in the severely low category, and 88% of those listed with an obese BMI%. Compared to patients with a normal listing BMI%, the cohort with severely low BMI% had worse overall survival regardless of LTx (p = 0.009) and graft survival (p = 0.034). Compared to patients with a low BMI%, those with a severely low BMI% had significantly poorer graft survival as well (p = 0.040). Mean graft survival was not significantly different between groups that remained at listing BMI% vs those that improved in category despite an overall small sample size. Independent predictors of poorer survival from the time of listing include severely low vs low-normal BMI% (HR = 1.20) and listing age (HR = 1.02). CONCLUSION: The proportion of children listed at severely low BMI% has steadily decreased with time, yet pediatric LTx candidates listed with a severely low BMI% had poorer graft and overall survival compared to those of normal BMI%. Severely low listing BMI% was an independent prognostic factor for higher mortality risk from the time of placement on the waitlist. BMI% may be a modifiable target for improving survival regardless of transplantation.

Lung Transplantation for Bronchopulmonary Dysplasia.

BACKGROUND: Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group. RESEARCH QUESTION: What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses? STUDY DESIGN AND METHODS: The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vs LTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio. RESULTS: BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs 57 [45-63] years; P < .001), and more were likely to receive mechanical ventilation at listing (23% vs 3.7%; P < .001). Patients with BPD had an FEV1 of 17% compared with 34% predicted in other patients (P = .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P = .106), even following propensity score matching (P = .41). INTERPRETATION: LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.

Longitudinal Assessment of Educational Risk for K-12 Students with Cystic Fibrosis.

OBJECTIVES: To assess the use of services provided by a cystic fibrosis (CF) center school specialist and evaluate relationships among student educational risk scores, family concerns for school engagement and performance, and disease severity. STUDY DESIGN: This was a retrospective review of medical records for 126 children with CF in grades K-12 who were screened for educational risk or used school intervention services during the 2017- 020 school years. Regression analyses were performed to identify and quantify predictors of educational risk, family concern for school performance and ability to advocate, and use of school specialist services. RESULTS: Most children with CF (62%-82%) were at moderate-to-high educational risk. Sixteen or more school absences, family concerns for their child's school performance or inability to advocate for their school needs, child mental health visits, and greater frequency of hospitalization predicted greater educational risk scores and more encounters with the school specialist. Better lung function and lower grade level were associated with lower educational risk. Number of encounters with the School Specialist remained high across three pre-coronavirus disease 2019 school years. CONCLUSIONS: Our experience illustrates a need to identify educational risk and support school experiences of children and youth with CF as a component of the care model. Tailored support, based on identification of risk predictors, has potential to improve educational outcomes.

Hyperpolarized 129Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases.

RATIONALE: There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP 129Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding. MATERIALS AND METHODS: HP 129Xe MRI was performed in a total of 176 subjects (125 pediatrics and 51 adults, age 20.98±16.48 years) who were either healthy controls (n = 23) or clinically diagnosed with cystic fibrosis (CF) (n = 37), lymphangioleiomyomatosis (LAM) (n = 29), asthma (n = 22), systemic juvenile idiopathic arthritis (sJIA) (n = 11), interstitial lung disease (ILD) (n = 7), or were bone marrow transplant (BMT) recipients (n = 47). HP 129Xe ventilation images were acquired during a ≤16 second breath-hold using a 2D multi-slice gradient echo sequence on a 3T Philips scanner (TR/TE 8.0/4.0ms, FA 10-12°, FOV 300 × 300mm, voxel size≈3 × 3 × 15mm). Images were analyzed using 5 different methods to quantify VDPs: linear binning (histogram normalization with binning into 6 clusters) following either linear or a variant of a nonparametric nonuniform intensity normalization algorithm (N4ITK) bias-field correction, thresholding ≤60% of the mean signal intensity with linear bias-field correction, and thresholding ≤60% and ≤75% of the mean signal intensity following N4ITK bias-field correction. Spirometry was successfully obtained in 84% of subjects. RESULTS: All quantification schemes were able to label visually identifiable ventilation defects in similar regions within all subjects. The VDPs of control subjects were significantly lower (p<0.05) compared to BMT, CF, LAM, and ILD subjects for most of the quantification methods. No one quantification scheme was better able to differentiate individual disease groups from the control group. Advanced statistical modeling of the VDP quantification schemes revealed that in comparing controls to the combined disease group, N4ITK bias-field corrected 60% thresholding had the highest predictive efficacy, sensitivity, and specificity at the VDP cut-point of 2.3%. However, compared to the thresholding quantification schemes, linear binning was able to capture and label subtle low-ventilation regions in subjects with milder obstruction, such as subjects with asthma. CONCLUSION: The difference in VDP between healthy controls and patients varied between the different disease states for all quantification methods. Although N4ITK bias-field corrected 60% thresholding was superior in separating the combined diseased group from controls, linear binning is able to better label low-ventilation regions unlike the current, 60% thresholding scheme. For future clinical trials, a consensus will need to be reached on which VDP scheme to utilize, as there are subtle advantages for each for specific disease.

Heliotropium indicum L.: From Farm to a Source of Bioactive Compounds with Therapeutic Activity.

This study aimed to summarize the available data on the ethnomedicinal and phytopharmacological activities of Heliotropium indicum L. based on database reports. For this purpose, an up-to-date literature search was carried out in the Google Scholar, Scopus, Springer Link, Web of Science, ScienceDirect, ResearchGate, PubMed, Chem Spider, Elsevier, BioMed Central, and patent offices (e.g., USPTO, CIPO, NPI, Google patents, and Espacenet) for the published materials. The findings suggest that the plant contains many important phytochemicals, including pyrrolizidine alkaloids, indicine, echinitine, supinine, heleurine, heliotrine, lasiocarpine, acetyl indicine, indicinine, indicine N-oxide, cynoglossine, europine N-oxide, heleurine N-oxide, heliotridine N-oxide, heliotrine N-oxide, heliotrine, volatile oils, triterpenes, amines, and sterols. Scientific reports revealed that the herb showed antioxidant, analgesic, antimicrobial, anticancer, antituberculosis, antiplasmodial, anticataract, antifertility, wound healing, antiinflammatory, antinociceptive, antihyperglycemic, anthelmintic, diuretic, antitussive, antiglaucoma, antiallergic, and larvicidal activity. In conclusion, in vitro studies with animal models seem to show the potential beneficial effects of H. indicum against a wide variety of disorders and as a source of phytotherapeutic compounds. However, clinical studies are necessary to confirm the effects observed in animal models, determine the toxicity of the therapeutic dose and isolate the truly bioactive components.

The maturation changes of sleep-related respiratory abnormalities in infants with laryngomalacia.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and central sleep apnea (CSA) are common in infants with laryngomalacia. The purpose of this study was to evaluate developmental changes in sleep-related breathing disorders over time in infants with laryngomalacia and understand the effect of supraglottoplasty (SGP) and nonsurgical treatment. METHODS: This is a retrospective review of infants with laryngomalacia who had at least 2 diagnostic polysomnography studies performed from January 2000 and May 2015. We included infants who had either OSA or CSA. Comparison of sleep and respiratory parameters by age group (0-6, 6-12, and >12 months old) was performed in both SGP and non-SGP groups using a mixed-effect regression model. A log-normal mixed model was used to explore the changes in sleep and respiratory parameters with age. The time to resolution of CSA and OSA was analyzed using nonparametric survival analysis. RESULTS: A total of 102 infants were included; 57 had only OSA and 45 had both CSA and OSA. There were significant decreases in apnea-hypopnea index, obstructive index, central apnea index, and arousal index with increasing age in both SGP and non-SGP groups. The mean age at resolution of CSA (central apnea index < 5) was 7.60 months old for SGP and 12.57 months old for non-SGP (P < .05). There were no significant differences in the mean age at resolution of OSA (obstructive index < 1; 35.18 [SGP] vs 41.55 months [non-SGP]; P = .60) between SGP and non-SGP groups. Infants with neurologic disease, congenital anomalies, or genetic syndromes required significantly more time to resolve OSA (28.12 [normal] vs 53.13 [neurological] vs 59.53 months [congenital anomalies and genetic]; P < .01). CONCLUSIONS: Both OSA and CSA improve in infants with laryngomalacia with increasing age regardless of SGP. The mechanism underlying these changes may involve airway growth and maturation of respiratory control. Time to resolution of OSA is affected by the presence of neurologic diseases, congenital anomalies, and genetic syndromes. Further studies are needed to confirm these findings and to evaluate long-term outcomes in this population.

Effect of Adenotonsillectomy on Cardiac Function in Children Age 5-13 Years With Obstructive Sleep Apnea.

Changes in left ventricular structure and function have been previously described in children with obstructive sleep apnea (OSA). We aimed to determine if these structural and functional cardiac changes are reversible after treatment of OSA with adenotonsillectomy. Children aged 5 to 13 years with OSA and matched healthy controls were recruited. Adenotonsillectomy occurred within 1 month after diagnosis. Echocardiography and polysomnography were repeated postoperatively. Linear mixed models were fitted to echocardiography measures at baseline and follow-up to assess the effect of OSA on cardiac structure and function. These adjusted for age, gender, race, body mass index, systolic, and diastolic blood pressure. The study sample included 373 children, 199 with OSA and 174 healthy controls. In the control group, 114 children completed the study and 112 completed the study in the OSA group. Children with OSA had reduced diastolic function, lower systolic function, and greater left ventricular mass index at baseline compared with healthy controls (all p < 0.05). Measures of active relaxation, elastic recoil and lengthening of the left ventricle impacted overall diastolic function; each of these worsened with increasing OSA severity. Postoperatively, diastolic function improved in children with OSA compared with controls. There were not significant changes in LV mass index or geometry. In conclusion, children with OSA have impaired left ventricular relaxation during diastole indicating early stage diastolic dysfunction. Adenotonsillectomy for OSA signficantly improved diastolic function. Left ventricular remodeling did not change with improvement of OSA.

Hepatoprotective and Antioxidant Capacity of Mallotus repandus Ethyl Acetate Stem Extract against d-Galactosamine-Induced Hepatotoxicity in Rats.

Mallotus repandus (M. repandus) is traditionally used to treat muscle pain, itching, fever, rheumatic arthritis, and a variety of liver disorders. The aim of the present work was to evaluate the hepatoprotective activity and the antioxidant potential of the ethyl acetate stem extract of M. repandus (ESMR) against d-galactosamine (d-GalN)-induced hepatopathy, along with a possible mechanism of action in rats. In vivo hepatoprotective activity of ESMR was examined using d-galactosamine (d-GalN)-induced hepatotoxicity in Sprague-Dawley rats. For this purpose, levels of serum diagnostic markers, activity of hepatic antioxidant enzymes, and liver histo-architecture were employed to assess the protective efficacy of ESMR. Furthermore, the total phenolic, flavonoid, and tannin contents were quantitated, and the antioxidant capacity of the extract was evaluated using different methods such as 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H2O2), and hydroxyl radical (OH•) scavenging assays. Intraperitoneal d-GalN injection triggered hepatotoxicity, as shown by the noticeable increase in the serum hepatic marker enzymes, bilirubin content, γ-glutamyl transferase (GGT), total cholesterol (TC), triglycerides (TGs), and malondialdehyde (MDA), whereas glutathione, superoxide dismutase, and catalase levels were significantly lower compared with that of the control. Pretreatment with ESMR reduced the hepatic enzyme levels along with bilirubin, GGT, and MDA compared to the d-GalN-intoxicated group. These results were supported by histopathological studies, where d-galactosamine caused coagulative necrosis, hemorrhage, and inflammation. However, pretreatment with ESMR ameliorated the histo-architectural changes and brought them back to normal. Results also revealed that the total polyphenolic, flavonoid, and tannin content, and total antioxidant capacity of ESMR were 136.30 ± 0.78 mg GAE/g mg, 38.72 ± 0.85 mg QE/g, 75.88 ± 0.54 mg TAE/g, and 123.16 ± 0.24 mg AAE/g, respectively. In addition, ESMR inhibited free radicals with IC50 values of 94.47 ± 0.51, 127.33 ± 0.36, 164.12 ± 0.45, and 254.14 ± 0.35 µg/mL in DPPH, NO, H2O2, and OH• free radical scavenging assays, respectively. These findings highlight the protective role of ESMR against hepatic injury induced by d-GalN, which may be attributed to its higher antioxidant properties, thereby scientifically justifying its traditional use.

Children with Down syndrome and mild OSA: treatment with medication versus observation.

STUDY OBJECTIVES: Children with Down syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA). Anti-inflammatory medications have been shown to be an effective treatment for mild OSA in otherwise healthy children. However, the efficacy in children with DS and mild OSA has not been investigated. Our aim was to examine the polysomnographic changes of children with DS and mild OSA treated with medication. METHODS: A retrospective chart review was performed in children with DS (< 18 years) and mild OSA (obstructive apnea-hypopnea index ≤ 5 events/h) diagnosed by polysomnography (PSG) between 2006 and 2018. Patients were included if they were treated with medications (intranasal corticosteroids and/or montelukast) or by observation with a duration of at least 3 months and had baseline and follow-up PSGs. Demographic data, comorbid diagnoses, and PSG data were collected and analyzed. RESULTS: Forty-five children met inclusion criteria. In the medication group, 29 children were identified. The median age was 7.4 years (interquartile range [IQR] 4.9-9.3). In the observation group, 16 children were identified. The median age was 4.0 years (IQR 3.2-5.3). The median time from baseline to follow-up PSG was 14.0 months (IQR 10.0-22.9) for the medication group and 10.5 months (IQR 6.5-33.5) for the observation group. There were no significant changes in the median obstructive apnea-hypopnea index from the baseline to follow-up PSG in either the medication group (2.8 [IQR 2.2-3.6) versus 3.5 [IQR 1.4-4.8) events/h; P = .25) or the observation group (2.3 [IQR 1.3-3.1] versus 2.9 [IQR 1.9-6.8] events/h; P = .12). Similarly, there were no significant differences in apnea-hypopnea index, oxygen nadir or end-tidal carbon dioxide between the groups (P = .07-1). CONCLUSIONS: In our cohort, medication therapy did not significantly improve polysomnographic measures in children with DS and mild OSA. Several factors such as hypotonia and relative macroglossia may explain the ineffectiveness of medical therapy for OSA in this population. Further prospective studies are necessary to confirm these results and to evaluate if a subgroup of DS children may benefit from medical therapy.

Hepatoprotective and Antioxidant Activities of Justicia gendarussa Leaf Extract in Carbofuran-Induced Hepatic Damage in Rats.

In folk medicines, Justicia gendarussa (J. gendarussa) is used as a depurative herb for treating fever, pain, and cancer and as laxative for constipation. The aim of the present investigation was to evaluate the hepatoprotective effect of the leaf methanol extract of J. gendarussa leaf (J gMe) against carbofuran (CF)-intoxicated liver injuries in Sprague-Dawley rats, along with the antioxidant activity of this extract. For this purpose, levels of serum diagnostic markers, hepatic antioxidant enzymes, and liver histo-architecture were employed to justify the protective efficacy of J gMe. In addition, the phenolic and flavonoid contents of the extract were quantified, and antioxidant activity was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays. Results revealed that the leaf extract caused a significant (<0.05, <0.01) decrease of the level of hepatic enzymes, triglycerides, and bilirubin and an increase of the total protein. J gMe has also significantly (<0.05, <0.01) lowered the level of malonylaldehyde. Carbofuran markedly suppressed hepatic antioxidant enzymes, however, the leaf extract significantly augmented these enzymes. The hepatoprotective effect was demonstrated by the improvement in the histo-architectural features of liver sections of CF-intoxicated rats treated with J gMe at 500 mg/kg dose. In addition, J gMe showed moderate total phenolic and total flavonoid content, whereas the IC50 values of DPPH, nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays were 71.31 ± 0.42, 134.82 ± 0.14, 47.69 ± 0.38, and 118.44 ± 0.30 µg/mL, respectively. In conclusion, the present study suggests the protective role of J gMe against hepatic injury induced by CF, which may be attributed to its higher antioxidant properties and thereby scientifically justifies its traditional use.

The effect of adenotonsillectomy on ventilatory control in children with obstructive sleep apnea.

STUDY OBJECTIVES: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in children and the effect of adenotonsillectomy are unknown. We aimed to examine the difference in ventilatory control between children with OSA and those without OSA. We also examined the effect of adenotonsillectomy on parameters of ventilatory control. METHODS: Healthy children with OSA and matched controls were recruited. Polysomnography was performed before adenotonsillectomy in the OSA group and 6 months postoperatively. Controls underwent the same assessment at the two time points. Loop gain (LG), controller gain (CG), and plant gain (PG), which reflect the stability of ventilatory control, chemoreceptor sensitivity and the pulmonary control of blood gas in response to a change in ventilation, respectively, were estimated from polysomnographic tracings which included spontaneous sighs and tracings with tidal breathing. A linear mixed model was used to examine the changes of the ventilatory control parameters from baseline to 6 months. RESULTS: Ninety-nine children aged 7-13 were recruited to the study. Fifty-three with OSA and 46 controls. At baseline, compared with controls, children with OSA had higher PG and lower CG. LG did not differ between groups. Six months following adenotonsillectomy, there was a significant decrease in PG in the OSA group, while no change observed in the control group. CONCLUSIONS: The study demonstrates that the pulmonary control of blood gas homeostasis is disturbed in children with OSA and it normalizes following adenotonsillectomy.

Management of Airway Obstruction in Infants With Pierre Robin Sequence.

BACKGROUND: Pierre Robin sequence (PRS)-related airway obstruction is often treated surgically; however, objective measures predicting the need for surgery are poorly defined. METHODS: A retrospective chart review was performed on 171 neonates with PRS. Infants were grouped based upon intervention modality: nonsurgical (conservative) or surgical [mandibular distraction osteogenesis (MDO) or tracheostomy]. Demographic data, physical examination findings, and study results were compared between groups to determine risk factors for surgical intervention, and to predict long-term success or failure of those interventions. RESULTS: The most significant, objective risk factor among those receiving surgery was a poor preintervention sleep study [obstructive index (OI): 42.4 versus 12.9 for the conservative treatment group; P < 0.001]. Only 11% of those treated conservatively had an OI >20, whereas 67.5% of those treated surgically met this severity measure. Of those receiving surgery, tracheostomy was associated with neurologic impairment (P = 0.030) and low birth weight (P = 0.046) compared with the MDO group. Together with syndromic status, these risk factors were useful for predicting failure of MDO to avoid subsequent tracheostomy (test sensitivity and specificity were 64.2% and 100.0%, respectively). No long-term differences in speech or micrognathia were detected between the 3 groups; however, those treated conservatively or with MDO had improved long-term feeding and airway obstruction outcomes compared with the tracheostomy group. CONCLUSIONS: Surgical intervention for PRS-related tongue-based airway obstruction should be strongly considered with an OI >20. Tracheostomy should be reserved for complex patients with concomitant syndromic diagnosis, neurologic impairment, and low birth weight.

Randomized Trial Evaluating the Effectiveness of Coloring on Decreasing Anxiety Among Parents in a Pediatric Surgical Waiting Area.

Anxiety is common among pediatric surgical patients and their parents. Numerous studies have examined interventions to reduce pediatric patients' anxiety; however, less is known about reducing parental anxiety. In other populations, producing art has been shown to significantly reduce anxiety. PURPOSE: This study aimed to determine whether parents' anxiety decreased after coloring while their child is in surgery. DESIGN AND METHODS: A block randomized controlled trial was conducted with a convenience sample of 106 parents of children who were having a scheduled surgery. Each day of data collection was randomized where all parents enrolled that day would either color a pre-drawn art template for 30min or would simply wait in the waiting room for 30min. The primary outcome measure was anxiety, measured by the 6-item short form of the Spielberger State Trait Anxiety Inventory (STAI). RESULTS: Parents' average anxiety score decreased from the initial measurement to the measurement 30min later in both the control group and the intervention group. The reduction in anxiety was significantly greater for those parents who participated in coloring during their wait (p<0.0001). CONCLUSIONS: Coloring is a creative, simple, low cost, and effective activity to reduce anxiety among parents in a pediatric surgical waiting area. PRACTICE IMPLICATIONS: Providing coloring materials and information about the benefits of coloring in pediatric surgery waiting areas is an easy to implement intervention to reduce parental anxiety.

Serum Cotinine and Hemoglobin A1c Among a National Sample of Adolescents Without Known Diabetes.

Introduction: National data suggest tobacco smoke is positively associated with higher glycated hemoglobin (HbA1c) among adults. Our objective was to examine the association between serum cotinine and HbA1c among adolescents without known diabetes. Methods: We assessed adolescents 12-19 years old (N = 11550) who participated in the 1999-2012 National Health and Nutrition Examination Survey. We applied sampling weights while performing multiple linear regression analyses. Results: The prevalence of serum cotinine indicative of no tobacco smoke exposure (TSE, <0.05 ng/mL) was 43.2%, passive TSE (0.05-2.99 ng/mL) was 38.9%, and active TSE (>3 ng/mL) was 17.9% in our sample. Mean (± standard error) HbA1c in participants with no TSE was 5.16% (±0.01), passive TSE was 5.16% (±0.01), and active TSE was 5.14% (±0.01). No differences in HbA1c were found between TSE groups including sex, age, race/ethnicity, education, income, and physical activity or the fully adjusted model with waist circumference. We found cotinine × sex (p = .01) and cotinine × age (p = .02) interactions. There was an association between cotinine and HbA1c for males but not females. Within males, participants with cotinine ≥3 ng/mL (5.26 ± 0.02) had higher mean HbA1c than those with cotinine 0.05-2.99 ng/mL and <0.05 ng/mL (both 5.20 ± 0.01, p ≤ .02). The negative association between age and HbA1c was stronger for participants with cotinine ≥3 ng/mL than participants with cotinine <0.05 ng/mL. Conclusion: No linear association was found between HbA1c and serum cotinine in adolescents overall after adjusting for potential confounders. Differences between TSE groups were found in males. Future research in adolescents should examine chronic TSE over time to examine the potential for development of type 2 diabetes. Implications: TSE has been associated with increased risk for the development of type 2 diabetes among adults. It is unclear if this relationship holds in adolescents. We examined the association between serum cotinine and HbA1c in adolescents without known diabetes who completed the 1999-2012 National Health and Nutrition Examination Survey. Although no association was found between serum cotinine and HbA1c overall while controlling for potential confounding factors, we observed interaction effects that are indicative of TSE influencing HbA1c differentially by sex and age. Reducing TSE in adolescents should be a priority for future tobacco control efforts.