The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction.

Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea, a global disease that is difficult to treat and for which there is no vaccine. This pathogen employs an arsenal of conserved outer membrane proteins called TonB-dependent transporters (TdTs) that allow the gonococcus to overcome nutritional immunity, the host strategy of sequestering essential nutrients away from invading bacteria to handicap infectious ability. N. gonorrhoeae produces eight known TdTs, of which four are utilized for acquisition of iron or iron chelates from host-derived proteins or xenosiderophores produced by other bacteria. Of the remaining TdTs, two of them, TdfH and TdfJ, facilitate zinc uptake. TdfH was recently shown to bind Calprotectin, a member of the S100 protein family, and subsequently extract its zinc, which is then internalized by N. gonorrhoeae. Like Calprotectin, other S100s are also capable of binding transition metals such as zinc and copper, and thus have demonstrated growth suppression of numerous other pathogens via metal sequestration. Considering the functional and structural similarities of the TdTs and of the S100s, as well as the upregulation in response to Zn limitation shown by TdfH and TdfJ, we sought to evaluate whether other S100s have the ability to support gonococcal growth by means of zinc acquisition and to frame this growth in the context of the TdTs. We found that both S100A7 and S10012 are utilized by N. gonorrhoeae as a zinc source in a mechanism that depends on the zinc transport system ZnuABC. Moreover, TdfJ binds directly to S100A7, from which it internalizes zinc. This interaction is restricted to the human version of S100A7, and zinc presence in S100A7 is required to fully support gonococcal growth. These studies highlight how gonococci co-opt human nutritional immunity, by presenting a novel interaction between TdfJ and human S100A7 for overcoming host zinc restriction.

Suppurative Thyroiditis: A Management Paradigm Based on Microbiology.

OBJECTIVE: The aim of this study was to determine if microbiological cultures can guide management of suppurative thyroiditis. DESIGN: This study is a retrospective case series set in 2 tertiary care academic hospitals. METHODS: The microbiological cultures from patients with suppurative thyroiditis who underwent incision and drainage from July 2004 to June 2018 were reviewed. Those who had confirmed pyriform sinus tracts and underwent surgical intervention were included in the study. RESULTS: Fifteen patients satisfied the criteria for inclusion. All had confirmed pyriform sinus tracts and underwent successful intervention. Endoscopic cautery was the most common intervention followed by complete open excision. Five cultures grew alpha Streptococcus, 6 had Eikenella, and 4 Prevotella. Combinations of Eikenella + Prevotella were seen in 3, and 1 sample had all 3 bacteria. Two cultured methicillin-susceptible Staphylococcus aureus alone. One culture was sterile. CONCLUSIONS: The presence of oral flora in an intrathyroidal abscess is confirmatory evidence of a pyriform sinus tract. Further investigations are not needed, and early definitive intervention can be planned.

Predicting polysomnographic severity thresholds in children using machine learning.

BACKGROUND: Approximately 500,000 children undergo tonsillectomy and adenoidectomy (T&A) annually for treatment of obstructive sleep disordered breathing (oSDB). Although polysomnography is beneficial for preoperative risk stratification in these children, its expanded use is limited by the associated costs and resources needed. Therefore, we used machine learning and data from potentially wearable sensors to identify children needing postoperative overnight monitoring based on the polysomnographic severity of oSDB. METHODS: Children aged 2-17 years undergoing polysomnography were included. Six machine learning models were created using (i) clinical parameters and (ii) nocturnal actigraphy and oxygen desaturation index. The prediction performance for polysomnography-derived severity of oSDB measured by apnea hypopnea index (AHI) >2 and >10 were evaluated. RESULTS: One hundred and ninety children were included. One hundred and eight were male (57%), mean age was 6.7 years [95% confidence interval; 6.1, 7.2], and mean AHI was 10.6 [7.8, 13.4]. Predictive performance utilizing clinical parameters was poor for both AHI > 2 (accuracy range: 48-56% for all models) and AHI > 10 (50-61%). Combining oximetry and actigraphy improved the accuracy to 87-89% for AHI > 2 and 95-96% for AHI > 10. CONCLUSIONS: Machine learning with oximetry and actigraphy identifies most children needing overnight monitoring as determined by polysomnographic severity of oSDB, supporting a potential resource-conscious screening pathway for children undergoing T&A. IMPACT: We provide proof of principle for the utility of machine learning, oximetry, and actigraphy to screen for severe obstructive sleep apnea syndrome (OSAS) in children. Clinical parameters perform poorly in predicting the severity of OSAS, which is confirmed in the current study. The predictive accuracy for severe OSAS was improved by a smaller subset of quantifiable physiologic parameters, such as oximetry. The results of this study support a lower cost, patient-friendly screening pathway to identify children in need of in-hospital observation after surgery.

Refining screening questionnaires for prediction of sleep apnea severity in children.

PURPOSE: Screening instruments are poor predictors of the severity of pediatric obstructive sleep apnea (OSA). We hypothesized that their performance could be improved by identifying and eliminating redundant features. METHODS: Baseline scores from three screening questionnaires for pediatric OSA were obtained from the Childhood Adenotonsillectomy Trial (CHAT). The questionnaires included the (i) modified Epworth sleepiness scale (ESS), (ii) the sleep-related breathing disorders subscale of the pediatric sleep questionnaire (PSQ), and the (iii) obstructive sleep apnea-18 (OSA-18) scale. Key features from each questionnaire were identified using variable selection methods. These selected features (SF) were then assessed for their ability to predict the severity of OSA, measured by the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). In addition, prediction performance of SF was also calculated for AHI > 5 and > 10 and ODI > 5 and > 10, respectively. RESULTS: Four hundred fifty-three children aged 5-10 years were included. The majority of the pairwise correlations among the items within the 3 screening questionnaires were statistically significant. The prediction of AHI and ODI by overall questionnaire scores was poor. Four-item SF, comprising apneic pauses, growth problems, mouth breathing, and obesity predicted AHI and ODI significantly better than each of the individual questionnaires. Furthermore, SF also predicted AHI > 5 and > 10, as well as ODI > 5 and > 10 significantly better than the original questionnaires. CONCLUSIONS: Elimination of redundant items in screening questionnaires improves their prediction performance for OSA severity in children with high pre-test probability for the condition.

An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated base excision repair products.

DNA glycosylases excise a broad spectrum of alkylated, oxidized, and deaminated nucleobases from DNA as the initial step in base excision repair. Substrate specificity and base excision activity are typically characterized by monitoring the release of modified nucleobases either from a genomic DNA substrate that has been treated with a modifying agent or from a synthetic oligonucleotide containing a defined lesion of interest. Detection of nucleobases from genomic DNA has traditionally involved HPLC separation and scintillation detection of radiolabeled nucleobases, which in the case of alkylation adducts can be laborious and costly. Here, we describe a mass spectrometry method to simultaneously detect and quantify multiple alkylpurine adducts released from genomic DNA that has been treated with N-methyl-N-nitrosourea (MNU). We illustrate the utility of this method by monitoring the excision of N3-methyladenine (3 mA) and N7-methylguanine (7 mG) by a panel of previously characterized prokaryotic and eukaryotic alkylpurine DNA glycosylases, enabling a comparison of substrate specificity and enzyme activity by various methods. Detailed protocols for these methods, along with preparation of genomic and oligonucleotide alkyl-DNA substrates, are also described.

Tracheal foreign bodies: are radiographs misleading?

OBJECTIVE: This study aimed to highlight the pitfalls of relying on radiographs in identifying potentially life-threatening upper airway foreign bodies in children. DESIGN: Case series. METHODS: A review of the medical records of 2 cases of upper tracheal foreign body was performed. RESULTS: Both patients presented with biphasic stridor refractory to medical therapy and chest radiographs that were normal. One patient had a history of witnessed aspiration while the other did not. Both patients were managed by endoscopic removal of foreign bodies in the operating room and experienced no long-term sequelae related to this event. CONCLUSIONS: Tracheal foreign bodies present a diagnostic challenge, and patients may fail to manifest radiographic abnormalities. In patients with a characteristic history and biphasic stridor, an endoscopic evaluation of the airway should be performed to avoid potentially devastating consequences.

Ultrasound versus fine needle aspiration for the initial evaluation of pediatric cervical lymphadenopathy-A systematic review.

OBJECTIVE: Cervical lymphadenopathy is a frequent finding in children that poses diagnostic challenges. We sought to compare the utility of fine needle aspiration (FNA) with ultrasound (US) for evaluating pediatric cervical lymphadenopathy based on published literature. STUDY DESIGN: In October 2019, we performed a comprehensive electronic search of PubMed, OVID (MEDLINE), EMBASE, and Scopus databases. Two authors independently screened and assessed full-text reports of potentially eligible studies. We compared sensitivity, specificity, positive predictive value estimates, and balanced accuracy for determining the underlying etiology of lymphadenopathy. RESULTS: The initial search returned 7736 possible studies, of which 31 met the criteria for inclusion. A total of 25 studies were included in the final analysis, with a total of 4721 patients, of which 52.8% were male. Of these, 9 (36.0%) examined US, and 16 (64%) examined fine needle aspiration. The pooled balanced accuracy for determining etiology was 87.7% for US and 92.9% for FNA. Reactive lymphadenopathy was identified in 47.9%, 9.2% were malignant, 12.6% were granulomatous, and 6.6% were non-diagnostic. CONCLUSIONS: In this systematic review, US was identified as an accurate initial diagnostic imaging modality in children. Fine needle aspiration was found to play a significant role in ruling out malignant lesions and potentially avoiding excisional biopsy.

Resting-State Cerebral Hemodynamics is Associated With Problem Behaviors in Pediatric Sleep-Disordered Breathing.

OBJECTIVE: Untreated sleep-disordered breathing (SDB) is associated with problem behaviors in children. The neurological basis for this relationship is unknown. We used functional near-infrared spectroscopy (fNIRS) to assess the relationship between cerebral hemodynamics of the frontal lobe of the brain and problem behaviors in children with SDB. STUDY DESIGN: Cross-sectional. SETTING: Urban tertiary care academic children's hospital and affiliated sleep center. METHODS: We enrolled children with SDB aged 5 to 16 years old referred for polysomnography. We measured fNIRS-derived cerebral hemodynamics within the frontal lobe during polysomnography. We assessed parent-reported problem behaviors using the Behavioral Response Inventory of Executive Function Second Edition (BRIEF-2). We compared the relationships between (i) the instability in cerebral perfusion in the frontal lobe measured fNIRS, (ii) SDB severity using apnea-hypopnea index (AHI), and (iii) BRIEF-2 clinical scales using Pearson correlation (r). A p < .05 was considered significant. RESULTS: A total of 54 children were included. The average age was 7.8 (95% confidence interval, 7.0-8.7) years; 26 (48%) were boys and 25 (46%) were Black. The mean AHI was 9.9 (5.7-14.1). There is a statistically significant inverse relationship between the coefficient of variation of perfusion in the frontal lobe and BRIEF-2 clinical scales (range of r = 0.24-0.49, range of p = .076 to <.001). The correlations between AHI and BRIEF-2 scales were not statistically significant. CONCLUSION: These results provide preliminary evidence for fNIRS as a child-friendly biomarker for the assessment of adverse outcomes of SDB.

Tracheostomy in the extremely premature neonate - Long term outcomes in a multi-institutional study.

OBJECTIVES: To describe the long-term outcomes related to breathing, feeding, and neurocognitive development in extremely premature infants requiring tracheostomy. STUDY DESIGN: Pooled cross-sectional survey. SETTING: Multi-institutional academic children's hospitals. METHODS: Extremely premature infants who underwent tracheostomy between January 1, 2012, and December 31, 2019, at four academic hospitals were identified from an existing database. Information was gathered from responses to a questionnaire by caregivers regarding airway status, feeding, and neurodevelopment 2-9 years after tracheostomy. RESULTS: Data was available for 89/91 children (96.8%). The mean gestational age was 25.5 weeks (95% CI 25.2-25.7) and mean birth weight was 0.71 kg (95% CI 0.67-0.75). Mean post gestational age at tracheostomy was 22.8 weeks (95% CI 19.0-26.6). At time of the survey, 18 (20.2%) were deceased. 29 (40.8%) maintained a tracheostomy, 18 (25.4%) were on ventilatory support, and 5 (7%) required 24-h supplemental oxygen. Forty-six (64.8%) maintained a gastrostomy tube, 25 (35.2%) had oral dysphagia, and 24 (33.8%) required a modified diet. 51 (71.8%) had developmental delay, 45 (63.4%) were enrolled in school of whom 33 (73.3%) required special education services. CONCLUSIONS: Tracheostomy in extremely premature neonates is associated with long term morbidity in the pulmonary, feeding, and neurocognitive domains. At time of the survey, about half are decannulated, with a majority weaned off ventilatory support indicating improvement in lung function with age. Feeding dysfunction is persistent, and a significant number will have some degree of neurocognitive dysfunction at school age. This information may help caregivers regarding expectations and plans for resource management.

Prospective validation of a brief questionnaire for predicting the severity of pediatric obstructive sleep apnea.

INTRODUCTION: Pediatric obstructive sleep apnea (OSA) is diagnosed and stratified by polysomnography. However, due to cost and inaccessibility, up to 90% of children undergo tonsillectomy and adenoidectomy (T&A) solely based on clinical criteria. We previously developed a data-driven brief screening questionnaire ('Selected Features,' SF) that predicted OSA severity than alternatives. The SF asks the parent whether a child: (i) has had breath-holding spells at night over the past 4 weeks, (ii) is a mouth-breather during the day, (iii) has stopped growing at a normal rate any time since birth, and (iv) is overweight. This study sought prospectively validate the SF questionnaire. METHODS: We conducted a prospective assessment of the predictive accuracy of SF compared to the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorder (PSQ-SRBD) scale in otherwise healthy children with sleep disordered breathing referred for T&A. We compared the model fits of PSQ-SRDB and SF for (i) a linear regression model for the prediction of OSA, and (ii) a logistic regression model for severe OSA, defined as apnea hypopnea index (AHI) > 10. P < 0.05 was significant. RESULTS: A total of 124 patients were included. The average age was 7.3 years (95% confidence interval, 6.6-8.0) and 66 (54%) were male. The racial composition was 54 (44%) black, 41 (33%) white, and 28 (23%) other. The median AHI was 4.8 (interquartile range 12) and 43 (35%) of patients had severe OSA. In linear and logistic regression models, SF outperformed the PSQ-SRBD and null models as measured by Akaike Information Criteria. The overall accuracy in predicting AHI >10 for PSQ-SRBD was 0.65 (0.56-0.73, P = 0.54) compared to 0.73 (0.64-0.80, P = 0.04) for SF. CONCLUSION: By eliminating redundancy, we have developed a questionnaire with improved prediction of OSA and its severity, in children with high pre-test probability of the condition. While multi-site validation is necessary, SF demonstrates value in screening children prior to T&A in resource-limited environments.

Bacterial tracheitis: a varied entity.

OBJECTIVE: The objective of the study was to highlight the different presentations of bacterial tracheitis (BT), a potential life-threatening cause of airway obstruction in children. DESIGN: Case series. METHODS: A review of medical records of 4 cases of BT who presented with differing signs and symptoms was performed. RESULTS: Clinical manifestations of 4 patients with BT are presented with corresponding endoscopic appearances of the airway. Two patients were afebrile and nontoxic, and 2 had an elevated white cell count. Three had different degrees of stridor. One had a respiratory arrest. Cultures grew Staphylococcus aureus in 2 and Moraxella catarrhalis in 1 and were mixed in 1 patient. None required intubation. All were successfully treated with antibiotics and bronchoscopic debridement of the membranes. CONCLUSIONS: Bacterial tracheitis needs a high index of suspicion because of its varied presentations. Certain forms have less severe clinical manifestations. These forms also require aggressive management as they can result in airway obstruction from membranes and edema.

Recovery After Adenotonsillectomy-Do Steroids Help? Outcomes From a Randomized Controlled Trial.

OBJECTIVES: The primary objective was to compare pain control following adenotonsillectomy (AT) in children with and without a single postoperative dose of oral dexamethasone in addition to standard analgesic medication. The secondary objective was to compare changes in caregiver-reported snoring, return to normal diet and baseline function, and the number of phone calls and emergency department (ED) visits. STUDY DESIGN: Prospective randomized controlled trial. SETTING: Tertiary care university hospital. METHODS: Children aged 3 to 10 years with sleep-disordered breathing who were scheduled to undergo AT were randomized to receive standard analgesia with or without dexamethasone (0.6 mg/kg) administered on the third postoperative day. Standard analgesia was defined as alternating weight-based doses of ibuprofen and acetaminophen. A nurse practitioner blinded to the study condition performed telephone surveys postoperatively, and the electronic medical record was reviewed. RESULTS: Enrollment comprised 149 children, of whom 119 were included. When compared with the control group (n = 61, 51%), children who received dexamethasone (n = 58, 49%) had a greater decrease in reported pain score on day 4 (mean ± SD, 2.5 ± 3.1 vs 1.1 ± 3.5, P < .001). Additionally, steroid use was associated with fewer caregiver phone calls (18 [29.5%] vs 6 [10%]) and ED visits (6 [10%] vs 1 [2%]). CONCLUSION: A single dose of dexamethasone administered on day 3 after adenotonsillectomy significantly improved pain control. There were fewer phone calls and ED visits in the steroid arm. These results support the use of oral steroids as an adjunct for postoperative pain control in children undergoing AT.

Adenochondroma of the Thyroid in a 3-Year-Old Female: A Case Report.

Follicular adenomas are the most common benign thyroid neoplasm but are unusual in children. However, other rare degenerative lesions and those of developmental origin can also present as thyroid masses. This article reports the first described pediatric thyroid adenochondroma. A 3-year-old female presented with a hard mass in the right lobe of her thyroid with nondiagnostic imaging and cytology findings. She underwent a right thyroid lobectomy uneventfully. Final histopathology examination confirmed an adenochondroma. To the best of our knowledge, an adenochondroma of the thyroid gland in a child has not been previously reported in literature. Though a rare and benign entity, thyroid adenochondromas present clinically with many features concerning for malignancy. Therefore, these lesions should be considered in the differential diagnosis of pediatric thyroid masses.

Baseline apnea-hypopnea index threshold and adenotonsillectomy consideration in children with OSA.

OBJECTIVES: Adenotonsillectomy (AT) is the first line of treatment for pediatric obstructive sleep apnea (OSA). In some treatment guidelines, children with moderate to severe OSA, defined as apnea-hypopnea index (AHI) ≥ 5, may be recommended AT regardless of symptoms. The differences in outcomes between children randomized to watchful waiting with supportive care (WWSC) or AT were compared based on baseline OSA severity threshold of AHI≥ 5. METHODS: A secondary analysis of the Childhood Adenotonsillectomy Trial, a randomized controlled trial of children with OSA aged 5-9 years who underwent AT or WWSC, was performed. The primary outcome was the change in neurocognition measured by Developmental Neuropsychological Assessment (NEPSY). Secondary outcomes included changes in behavior, symptoms of OSA, and quality of life. Outcomes were measured at baseline and the seven-month follow-up after grouping children based on whether their AHI was greater than or equal to 5. Comparisons were performed using two-way analysis of covariance (ANCOVA) while controlling for age, sex and race. Differences in treatment effect were measured using Cohen's d. RESULTS: Of the 397 children included, 203 received WWSC and 194 underwent AT. The treatment effects on post-randomization changes in neurocognition, measured by NEPSY in children with AHI ≥5 (Cohen's d = 0.1 [95% CI, -0.1 to 0.4]) was not significantly different from children with AHI <5 (Cohen's d = 0.1 [95% CI, -0.1 to 0.4]). Furthermore, among children in the AT group alone, the effects of AT on post-treatment changes in NEPSY did not differ based on AHI threshold (Cohen's d = -0.06 [95% CI, -0.3 to 0.2]). Additionally, the treatment effects on post-randomization changes in behavior, symptoms, and quality of life did not vary based on AHI threshold. CONCLUSION: The outcomes of neurocognition, behavior, symptoms, and quality of life did not differ between children with OSA randomized to WWSC or AT based on OSA severity threshold alone. Additionally, the effects of AT on post-treatment outcomes did not differ based on AHI threshold.

Tracheostomy on infants born in the periviable period: Outcomes at discharge from the neonatal intensive care unit (NICU).

OBJECTIVES: Advances in neonatal intensive care have allowed successful resuscitation of children born at the border of viability. However, there has been little change in the incidence of bronchopulmonary dysplasia (BPD) and anatomical upper airway obstruction which may require a tracheostomy in that group. The benefits of the procedure are accompanied by sequelae that impact outcomes. Information about these issues can assist caregivers in making decisions and planning care after discharge from the neonatal intensive care unit (NICU). The objectives of this study were to describe the clinical characteristics of neonates born in the periviable period (≤25 weeks gestation) requiring tracheotomy and to highlight their hospital course, complications and status upon NICU discharge. METHODS: Retrospective analysis at four tertiary care academic children's hospitals. Medical records of neonates born ≤25 weeks gestation who required tracheotomy between January 1, 2012 and December 31, 2018 were reviewed. Demographics, medical comorbidities, and tracheostomy related complications were studied. Feeding, ventilation, and neurodevelopmental outcomes at time of transfer from NICU were evaluated. RESULTS: Fifty-two patients were included. The mean gestational age was 24.3 (95% confidence interval, 24.1 to 24.5) weeks. The mean birth weight was 635 (95% CI: 603 to 667) grams and 50 (96.2%) children had BPD. At time of discharge from the NICU, 47 (90.4%) required mechanical ventilation, four (7.7%) required supplemental oxygen and one (1.9%) was weaned to room air. Forty-two (80.8%) were discharged with a gastrostomy tube, seven (28%) with a nasogastric tube, and three (5.8%) were on oral feeds. Two (3.8%) suffered hypoxic ischemic encephalopathy, 27 (51.9%) had neurodevelopmental delay, seven (13.5%) were diagnosed with another anomaly, and 16 (30.8%) were considered normal. Complications related to the procedure were observed in 28 (53.8%) neonates. Granulation tissue was seen in 17 (32.7%), wound break down or cellulitis in three (5.8%), one (1.9%) with tracheostomy plugging, three (5.8%) with dislodgement of the tracheostomy tube and four (7.7%) developed tracheitis. CONCLUSIONS: Tracheostomy in infants born in the periviable period is primarily performed for BPD and portends extended ventilatory dependence. It is associated with non-oral alimentation at the time of discharge from the NICU and developmental delay. Mortality directly related to the procedure is rare. Minor complications are common but do not require surgical intervention. These data may aid in counseling caregivers about the procedure in this vulnerable population.

Predictors of Behavioral Changes After Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Adenotonsillectomy (AT) is associated with improved behavior in children with obstructive sleep apnea (OSA). However, it is unknown whether polysomnographic parameters are superior to the parent-reported severity of sleep-disordered breathing (SDB) in predicting behavioral changes after AT. Objective: To ascertain whether polysomnographic parameters vs parent-reported severity of SDB are better predictors of treatment-related behavioral changes in children with OSA. Design, Setting, and Participants: This ad hoc secondary analysis of the Childhood Adenotonsillectomy Trial (CHAT) downloaded and analyzed data from January 1 to January 31, 2020. Children aged 5 to 9 years with a polysomnographic diagnosis of OSA were enrolled in the CHAT and subsequently randomized to undergo either early AT or watchful waiting with supportive care. All outcome measures were obtained at baseline and at follow-up (7 months after randomization). Interventions: Early AT vs watchful waiting with supportive care. Main Outcomes and Measures: Postrandomization changes between the baseline and follow-up periods were derived from (1) T scores in 4 validated behavioral assessments (Conners Global Index parent and teacher versions, Behavior Rating Inventory of Executive Function metacognition index, and Child Behavior Checklist of total, internalizing, and externalizing behavior subscales); (2) 8 aggregated polysomnographic parameters representing the severity of obstruction, hypoxemia, sleep quality, and structure; and (3) the parent-reported severity of SDB measured by the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder (PSQ-SRBD) scale. The treatment-related changes in each of the behavioral outcomes attributable to changes in SDB severity (represented by the subjective PSQ-SRBD score and objective polysomnographic parameters) were measured and compared using mediation analysis. Results: A total of 453 children were assessed at baseline, of whom 234 were girls (52%) and the mean (SD) age was 6.6 (1.4) years. The postrandomization changes in 7 of 8 behavioral outcome measures between the baseline and follow-up periods were partially mediated by the changes in PSQ-SRBD scores (range of nonzero causally mediated effects, 2.4-3.5), without contribution from any of the polysomnographic parameters. Conclusions and Relevance: This secondary analysis of a national randomized clinical trial found that most treatment-related behavioral changes in children with OSA were mediated by the changes in parent-reported SDB severity alone. These findings suggest that polysomnographic parameters provide clinicians with limited means to predict the improvement in neurobehavioral morbidity in OSA. Trial Registration: ClinicalTrials.gov Identifier: NCT00560859.

Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast.

Ubiquitination regulates many different cellular processes, including protein quality control, membrane trafficking, and stress responses. The diversity of ubiquitin functions in the cell is partly due to its ability to form chains with distinct linkages that can alter the fate of substrate proteins in unique ways. The complexity of the ubiquitin code is further enhanced by post-translational modifications on ubiquitin itself, the biological functions of which are not well understood. Here, we present genetic and biochemical evidence that serine 57 (Ser57) phosphorylation of ubiquitin functions in stress responses in Saccharomyces cerevisiae, including the oxidative stress response. We also identify and characterize the first known Ser57 ubiquitin kinases in yeast and human cells, and we report that two Ser57 ubiquitin kinases regulate the oxidative stress response in yeast. These studies implicate ubiquitin phosphorylation at the Ser57 position as an important modifier of ubiquitin function, particularly in response to proteotoxic stress.

Treatment-Related Changes in Heart Rate Variability in Children with Sleep Apnea.

OBJECTIVE: Heart rate variability (HRV), a noninvasive indicator of autonomic regulation of cardiac rhythm, may represent the physiologic burden of obstructive sleep apnea (OSA). We hypothesized that the treatment-related effects of OSA on HRV in children are causally attributable to the improvement in OSA severity. STUDY DESIGN: Secondary analysis of outcomes from the Childhood Adenotonsillectomy Trial (CHAT). SETTING: Analysis of database. SUBJECTS AND METHODS: Time- and frequency-domain HRV parameters along with polysomnographic (PSG) and demographic variables were obtained from the CHAT study, which compared early adenotonsillectomy (eAT) to watchful waiting (WW) in children with OSA. The relative contributions of PSG variables and covariates to each HRV parameter were quantified. The proportion of changes in HRV parameters causally attributable to changes in OSA severity, measured by the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), was estimated. RESULTS: In total, 404 children aged 5 to 10 years were included. The median (interquartile range) age was 6 (3-9) years. The median body mass index percentile was 82 (53), 195 (48%) children were male, and 147 (36%) were African American. The average heart rate during PSG was the strongest independent predictor of each HRV parameter (P < .001). Although eAT resulted in statistically significant changes in the majority of HRV parameters, these effects were not causally attributable to treatment-related changes in AHI or ODI. CONCLUSIONS: The average heart rate strongly modulates HRV in children with OSA. Although eAT results in discernible changes in HRV, it appears to not be causally attributable to specific treatment-related changes in AHI or ODI.

Ultrasonic-assisted extraction and digestion of proteins from solid biopsies followed by peptide sequential extraction hyphenated to MALDI-based profiling holds the promise of distinguishing renal oncocytoma from chromophobe renal cell carcinoma.

A novel analytical approach is proposed to discriminate between solid biopsies of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). The method comprises the following steps: (i) ultrasonic extraction of proteins from solid biopsies, (ii) protein depletion with acetonitrile, (iii) ultrasonic assisted in-solution digestion using magnetic nanoparticle with immobilized trypsin, (iv) C18 tip-based preconcentration of peptides, (v) sequential extraction of the peptides with ACN, (vi) MALDI-snapshot of the extracts and (vii) investigation of the extract containing the most discriminating features using high resolution mass spectrometry. With this approach we have been able to differentially cluster renal oncocytoma and chromophobe renal cell carcinoma and identified 18 proteins specific to chromophobe and seven unique to renal oncocytoma. Chromophobes express proteins associated with ATP function (ATP5I & 5E; VATE1 & G2; ADT2), glycolysis (PGK1) and neuromedin whilst oncocytomas express ATP5H, ATPA, DEPD7 and TRIPB thyroid receptor interacting protein.

Tracheostomy in the Extremely Premature Neonate: A Multi-Institutional Study.

OBJECTIVE: (1) To describe characteristics associated with tracheostomy placement and (2) to describe associated in-hospital morbidity in extremely premature infants. STUDY DESIGN: Pooled retrospective analysis of charts. SETTING: Academic children's hospitals. SUBJECTS AND METHODS: The patient records of premature infants (23-28 weeks gestational age) who underwent tracheostomy between January 1, 2012, and December 31, 2017, were reviewed from 4 academic children's hospitals. Demographics, procedural morbidity, feeding, respiratory, and neurodevelopmental outcomes at the time of transfer from the neonatal intensive care unit (NICU) were obtained. The contribution of baseline characteristics to mortality, neurodevelopmental, and feeding outcomes was also assessed. RESULTS: The charts of 119 infants were included. The mean gestational age was 25.5 (95% confidence interval, 25.2-25.7) weeks. The mean birth weight was 712 (671-752) g. Approximately 50% was African American. The principal comorbidity was chronic lung disease (92.4%). Overall, 60.5% of the infants had at least 1 complication. At the time of transfer, most remained mechanically ventilated (94%) and dependent on a feeding tube (90%). Necrotizing enterocolitis increased the risk of feeding impairment (P = .002) and death (P = .03). CONCLUSIONS: Tracheostomy in the extremely premature neonate is primarily performed for chronic lung disease. Complications occur frequently, with skin breakdown being the most common. Placement of a tracheostomy does not seem to mitigate the systemic morbidity associated with extreme prematurity.