Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 79
Filter
1.
Eur J Pediatr ; 183(6): 2663-2669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38507064

ABSTRACT

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease.  Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study.


Subject(s)
Hospitalization , Respiratory Syncytial Virus Infections , Humans , Male , Infant , Retrospective Studies , Female , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/therapy , Hospitalization/statistics & numerical data , Bronchiolitis, Viral/complications , Bronchiolitis, Viral/therapy , Length of Stay/statistics & numerical data , Body Weight , Thinness/epidemiology , Infant, Newborn , Risk Factors , Severity of Illness Index , Intensive Care Units, Pediatric/statistics & numerical data
3.
Arch Dis Child ; 109(5): 428-431, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38296613

ABSTRACT

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.


Subject(s)
Ciliary Motility Disorders , Genetic Testing , Humans , Consanguinity , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/genetics , Mutation
4.
Pediatr Pulmonol ; 58(2): 425-432, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36224102

ABSTRACT

BACKGROUND: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been a decline in pediatric emergency department visits. Our aim was to assess the pattern of pediatric foreign body aspiration (FBA) during the first year of the COVID-19 pandemic, in comparison to the prior years. METHODS: In this retrospective multicenter study, we compared the number of children who presented with FBA during the COVID-19 year (March 1, 2020 to February 28, 2021) to the annual average of the years 2016-2019. We also compared the lockdown periods to the postlockdown periods, and the percentage of missed FBA, proven FBA, and flexible bronchoscopy as the removal procedure. RESULTS: A total of 345 children with FBA from six centers were included, 276 in the pre-COVID-19 years (average 69 per year) and 69 in the COVID-19 year. There was no difference in the prevalence of FBA between the COVID-19 year and any of the prior 4 years. Examining the lockdown effect, the monthly incidence of FBA dropped from a pre-COVID-19 average of 5.75 cases to 5.1 cases during lockdown periods and increased to 6.3 cases in postlockdown periods. No difference in the percentage of missed FB or proven FB was observed. There was a significant rise in the usage of flexible bronchoscopy as the removal procedure (average of 15.4% vs. 30.4%, p = 0.001). CONCLUSION: There were fewer cases of pediatric FBA during lockdown periods, compared to post-lockdown periods, presumably related to better parental supervision, with no difference in the prevalence of FBA during the COVID-19 year.


Subject(s)
COVID-19 , Foreign Bodies , Child , Humans , Pandemics , Israel/epidemiology , Respiratory Aspiration/epidemiology , COVID-19/epidemiology , Communicable Disease Control , Bronchoscopy/methods , Retrospective Studies , Foreign Bodies/epidemiology
5.
Cell Rep ; 40(12): 111367, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36130495

ABSTRACT

Sleep spindles are crucial for learning in the cortex and basal ganglia (BG) because they facilitate the reactivation of previously active neuronal ensembles. Studying field potentials (FPs) and spiking in the cortex and BG during sleep in non-human primates following pre-sleep learning, we show that FP sleep spindles are widespread in the BG and are similar to cortical spindles in morphology, spectral content, and response to the pre-sleep task. Further, BG spindles are concordant with electroencephalogram (EEG) spindles and associated with increased cortico-BG correlation. However, spindles across the BG differ markedly in their entrainment of local spiking. The spiking activity of striatal projection neurons exhibits consistent phase locking to striatal and EEG spindles, producing phase windows of peaked cross-region spindling. In contrast, firing in other BG nuclei is not entrained to either local or EEG sleep spindles. These results suggest corticostriatal synapses as the main hub for offline cortico-BG communication.


Subject(s)
Basal Ganglia , Sleep , Animals , Basal Ganglia/physiology , Cerebral Cortex/physiology , Corpus Striatum , Electroencephalography , Neurons/physiology , Sleep/physiology
6.
Commun Biol ; 5(1): 612, 2022 06 21.
Article in English | MEDLINE | ID: mdl-35729350

ABSTRACT

Spontaneous pauses in firing are the hallmark of external pallidum (GPe) neurons. However, the role of GPe pauses in the basal ganglia network remains unknown. Pupil size and saccadic eye movements have been linked to attention and exploration. Here, we recorded GPe spiking activity and the corresponding pupil sizes and eye positions in non-human primates. We show that pauses, rather than the GPe discharge rate per se, were associated with dilated pupils. In addition, following pause initiation there was a considerable increase in the rate of spontaneous saccades. These results suggest that pauses are a powerful mechanism by which the GPe may influence basal ganglia downstream structures and play a role in exploratory behavior.


Subject(s)
Exploratory Behavior , Globus Pallidus , Animals , Basal Ganglia , Globus Pallidus/physiology , Neurons/physiology , Saccades
7.
Exp Neurol ; 350: 113976, 2022 04.
Article in English | MEDLINE | ID: mdl-35026228

ABSTRACT

Sleep disorders are integral to Parkinson's disease (PD). Insomnia, an inability to maintain stable sleep, affects most patients and is widely rated as one of the most debilitating facets of this disease. PD insomnia is often perceived as a multifactorial entity - a consequence of several of the disease symptoms, comorbidities and therapeutic strategies. Yet, this view evolved against a backdrop of a relative scarcity of works trying to directly dissect the underlying neural correlates and mechanisms in animal models. The last years have seen the emergence of a wealth of new evidence regarding the neural underpinnings of insomnia in PD. Here, we review early and recent reports from patients and animal models evaluating the etiology of PD insomnia. We start by outlining the phenomenology of PD insomnia and continue to analyze the evidence supporting insomnia as emanating from four distinct subdivisions of etiologies - the symptoms and comorbidities of the disease, the medical therapy, the degeneration of non-dopaminergic cell groups and subsequent alterations in circadian rhythms, and the degeneration of dopaminergic neurons in the brainstem and its resulting effect on the basal ganglia. Finally, we review emerging neuromodulation-based therapeutic avenues for PD insomnia.


Subject(s)
Parkinson Disease/complications , Sleep Initiation and Maintenance Disorders/etiology , Animals , Disease Models, Animal , Dopaminergic Neurons/pathology , Humans , Models, Animal , Nerve Degeneration , Parkinson Disease/physiopathology , Sleep Initiation and Maintenance Disorders/physiopathology
8.
Pediatr Pulmonol ; 56(12): 3983-3990, 2021 12.
Article in English | MEDLINE | ID: mdl-34499813

ABSTRACT

BACKGROUND: Little known about the prevalence of obstructive sleep apnea (OSA) in morbid obese adolescents and the association between OSA and comorbid factors. AIM: To examine the association between apnea-hypopnea index (AHI, a measure for OSA severity) and metabolic morbidity among morbidly obese adolescents. METHODS: We performed a population-based retrospective cohort study by reviewing sleep study, metabolic indices, and comorbidity-related data of a cohort (n = 106) of adolescents referred to a bariatric surgery clinic. We compared subjects with moderate/severe OSA (AHI ≥ 5) versus no/mild OSA (AHI < 5) OSA and three groups of subjects with increasing body mass index (BMI) concerning sleep-study and metabolic indices using univariate analyses. To assess the link between AHI and ferritin levels a multivariate linear regression (adjusted for BMI and mean cell volume) was preformed. RESULTS: A total of 71 patients met the inclusion criteria. Subjects with moderate/severe OSA (n = 32, 45%) had higher BMI, cholesterol, cholesterol/high-density lipoprotein (HDL) ratio, hemoglobin A1c, and serum ferritin levels (p < .05). AHI significantly increased across BMI strata (p = .02). Multivariate linear regression indicated that moderate/severe OSA was associated with higher levels of ferritin, unstandardized ß = 49.1 (nIU/ml) (p = .025). CONCLUSIONS: Morbidly obese adolescents with moderate/severe OSA versus no/mild OSA have a higher risk for metabolic complications. Therefore, OSA management should be considered in adolescents with morbid obesity, in addition to weight loss.


Subject(s)
Metabolic Diseases , Obesity, Morbid , Pediatric Obesity , Sleep Apnea, Obstructive , Adolescent , Body Mass Index , Humans , Metabolic Diseases/epidemiology , Metabolic Diseases/etiology , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Retrospective Studies , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology
9.
Sci Rep ; 10(1): 22115, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33335174

ABSTRACT

Obstructive sleep apnea syndrome (OSA) is associated with cardiovascular morbidity in adults and children. NFκB activity is enhanced in circulating monocytes of adults with OSA, that decreases following positive pressure therapy. OSA children's serum activates NFκB in a cell line. We hypothesized that OSA children's serum can activate NFκB in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NFκB in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls. Increased expression of NFκB classical subunits p65/p50 as well as major morphological changes occurred in cardiomyocytes following OSA's serum exposure. OSA children's serum induced NFκB activity as measured by p65 nuclear translocation in immortalized human CM and rat cardiomyocytes as well as dense immunostaining of the nucleus. Trypan blue and XTT assays showed that OSA sera induced CM apoptosis. We conclude that NFκB is systemically activated in cardiomyocytes, who also demonstrate decreased viability and contractility following exposure to OSA serum. It supports the hypothesis NFκB plays a role in the evolution of cardiovascular morbidity in OSA. It may support the search for new therapeutic interventions controlling NFκB activation in OSA.


Subject(s)
Myocytes, Cardiac/metabolism , NF-kappa B/metabolism , Sleep Apnea, Obstructive/metabolism , Biomarkers , Child , Female , Humans , Immunohistochemistry , Male , Signal Transduction , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/etiology
10.
Obes Res Clin Pract ; 14(6): 542-547, 2020.
Article in English | MEDLINE | ID: mdl-33189604

ABSTRACT

OBJECTIVES: To assess the association between sleep disorders prevalence and obesity in Israeli adolescents. METHODS: A nationwide, population-based, cross-sectional study of 1,348,817 Israeli adolescents (57% males) who were medically examined prior to military service between 1997 and 2015; height and weight were measured along with assessment of medical status at age 17.3⬰±â¬°0.4 years. The diagnosis of a sleep disorder was made based on objective diagnostic criteria. The prevalence and odds ratio (OR) for a sleep disorder were computed across BMI subgroups and were adjusted for socio-demographic confounders. RESULTS: Overall sleep disorders prevalence was 1.8:1000 (males) and 0.45:1000 (females), with a total of 1601 cases. There was a gradual increase in the odds ratio for sleep disorders with increasing BMI. Multivariable-adjusted ORs for sleep disorders were 1.29 (95% CI 1.10⬜1.52), 1.44 (1.18⬜1.75), 3.03 (2.32⬜3.96) and 3.38 (1.98⬜5.75) for overweight, obese class I, II and III, respectively (5th⬜49th BMI percentile was the reference). Results persisted in extensive sensitivity analyses including limiting the study sample to participants with unimpaired health. CONCLUSIONS: We found a higher prevalence of sleep disorders in males and a dose-dependent association between sleep disorders and adolescent BMI in both sexes. Our findings warrant clinical awareness among healthcare providers, given the rise in obesity in teenagers, and particularly in light of the obesity epidemic that we are experiencing in this era. Sleep related complaints should be actively screened in adolescents who suffer obesity.


Subject(s)
Obesity , Sleep Wake Disorders , Adolescent , Body Mass Index , Cross-Sectional Studies , Female , Humans , Male , Overweight , Prevalence
11.
J Clin Sleep Med ; 16(10): 1731-1735, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32638701

ABSTRACT

STUDY OBJECTIVES: Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition. Little is known about sleep/wake and slow-wave activity in this condition, although the central hypothalamic dysfunction associated with autonomic dysregulation would make the occurrence of SWA deregulation most likely. METHODS: Two children with clinical presentation of ROHHAD syndrome were evaluated, diagnosed, and treated. Their polysomnographic studies were compared with 4 matched children with obstructive sleep apnea and 6 controls. RESULTS: Children that were clinically diagnosed with ROHHAD exhibited significantly weaker slow-wave activity power and shallower slow-wave activity slopes during the first 2 sleep cycles compared with children with obstructive sleep apnea or controls. CONCLUSIONS: This study shows that children with ROHHAD have suppressed slow-wave activity, possibly because of hypothalamic dysregulation that may contribute to their rapid-onset obesity and excessive daytime sleepiness.


Subject(s)
Autonomic Nervous System Diseases , Hypothalamic Diseases , Obesity Hypoventilation Syndrome , Sleep, Slow-Wave , Autonomic Nervous System Diseases/complications , Child , Humans , Hypothalamic Diseases/complications , Hypoventilation/complications , Obesity/complications
12.
Proc Natl Acad Sci U S A ; 117(29): 17359-17368, 2020 07 21.
Article in English | MEDLINE | ID: mdl-32636265

ABSTRACT

Sleep disorders are among the most debilitating comorbidities of Parkinson's disease (PD) and affect the majority of patients. Of these, the most common is insomnia, the difficulty to initiate and maintain sleep. The degree of insomnia correlates with PD severity and it responds to treatments that decrease pathological basal ganglia (BG) beta oscillations (10-17 Hz in primates), suggesting that beta activity in the BG may contribute to insomnia. We used multiple electrodes to record BG spiking and field potentials during normal sleep and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in nonhuman primates. MPTP intoxication resulted in severe insomnia with delayed sleep onset, sleep fragmentation, and increased wakefulness. Insomnia was accompanied by the onset of nonrapid eye movement (NREM) sleep beta oscillations that were synchronized across the BG and cerebral cortex. The BG beta oscillatory activity was associated with a decrease in slow oscillations (0.1-2 Hz) throughout the cortex, and spontaneous awakenings were preceded by an increase in BG beta activity and cortico-BG beta coherence. Finally, the increase in beta oscillations in the basal ganglia during sleep paralleled decreased NREM sleep, increased wakefulness, and more frequent awakenings. These results identify NREM sleep beta oscillation in the BG as a neural correlate of PD insomnia and suggest a mechanism by which this disorder could emerge.


Subject(s)
Basal Ganglia/physiopathology , Parkinson Disease/complications , Sleep Initiation and Maintenance Disorders/complications , Sleep/physiology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Animals , Beta Rhythm/physiology , Cerebral Cortex/pathology , Haplorhini , Humans , Parkinson Disease/physiopathology , Sleep Initiation and Maintenance Disorders/physiopathology , Wakefulness
13.
Nat Neurosci ; 23(4): 556-564, 2020 04.
Article in English | MEDLINE | ID: mdl-32231338

ABSTRACT

Reinforcement learning models treat the basal ganglia (BG) as an actor-critic network. The ventral pallidum (VP) is a major component of the BG limbic system. However, its precise functional roles within the BG circuitry, particularly in comparison to the adjacent external segment of the globus pallidus (GPe), remain unexplored. We recorded the spiking activity of VP neurons, GPe cells (actor) and striatal cholinergic interneurons (critic) while monkeys performed a classical conditioning task. Here, we report that VP neurons can be classified into two distinct populations. The persistent population displayed sustained activation following visual cue presentation, was correlated with monkeys' behavior and showed uncorrelated spiking activity. The transient population displayed phasic synchronized responses that were correlated with the rate of learning and the reinforcement learning model's prediction error. Our results suggest that the VP is physiologically different from the GPe and identify the transient VP neurons as a BG critic.


Subject(s)
Action Potentials/physiology , Basal Forebrain/physiology , Basal Ganglia/physiology , Nerve Net/physiology , Neurons/physiology , Reinforcement, Psychology , Animals , Chlorocebus aethiops , Conditioning, Classical/physiology , Female , Models, Neurological
14.
Proc Natl Acad Sci U S A ; 115(18): E4274-E4283, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29666271

ABSTRACT

Slow oscillations of neuronal activity alternating between firing and silence are a hallmark of slow-wave sleep (SWS). These oscillations reflect the default activity present in all mammalian species, and are ubiquitous to anesthesia, brain slice preparations, and neuronal cultures. In all these cases, neuronal firing is highly synchronous within local circuits, suggesting that oscillation-synchronization coupling may be a governing principle of sleep physiology regardless of anatomical connectivity. To investigate whether this principle applies to overall brain organization, we recorded the activity of individual neurons from basal ganglia (BG) structures and the thalamocortical (TC) network over 70 full nights of natural sleep in two vervet monkeys. During SWS, BG neurons manifested slow oscillations (∼0.5 Hz) in firing rate that were as prominent as in the TC network. However, in sharp contrast to any neural substrate explored thus far, the slow oscillations in all BG structures were completely desynchronized between individual neurons. Furthermore, whereas in the TC network single-cell spiking was locked to slow oscillations in the local field potential (LFP), the BG LFP exhibited only weak slow oscillatory activity and failed to entrain nearby cells. We thus show that synchrony is not inherent to slow oscillations, and propose that the BG desynchronization of slow oscillations could stem from its unique anatomy and functional connectivity. Finally, we posit that BG slow-oscillation desynchronization may further the reemergence of slow-oscillation traveling waves from multiple independent origins in the frontal cortex, thus significantly contributing to normal SWS.


Subject(s)
Basal Ganglia/physiology , Biological Clocks/physiology , Brain Waves/physiology , Membrane Potentials/physiology , Nerve Net/physiology , Sleep/physiology , Animals , Chlorocebus aethiops , Female
15.
Pediatr Pulmonol ; 53(1): 95-102, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29178284

ABSTRACT

AIM: The aims of this pilot study were to determine safety, tolerability (primary outcome) and efficacy (secondary outcome) of high-dose inhaled nitric oxide for the treatment of infants with moderately severe bronchiolitis. METHODS: This was a pilot, double-blinded, randomized controlled study (phase IIa). Intermittent inhalations of nitric oxide 160 ppm for 30 min or oxygen/air (control) were given 5 times/day to hospitalized infants (2-11 months) with acute bronchiolitis. Oxygen saturation, methemoglobin, and nitric dioxide (NO2 ) levels and vital signs were monitored. RESULTS: Forty-three infants were enrolled. Baseline characteristics were comparable in both study groups. Mean clinical score, comprised of four components: respiratory rate, use of accessory muscles, wheezes and crackles, and % room-air oxygen saturation, was 7.86 (±1.1) and 8.09 (±1.2) in the NO and control groups, respectively, consistent with moderate severity. The overall frequency of adverse events was similar between the groups. Repeated nitric oxide inhalations did not result in increased inhaled NO2 levels or cumulative effect on methemoglobin levels. Secondary outcomes of efficacy were measured by length of hospitalization (LOS) in hours: LOS did not differ between groups. However, in a post-hoc analysis of a subgroup of infants hospitalized for >24 h (n = 24), the median LOS was shorter in the nitric oxide (41.9 h) than in the control group (62.5 h) (P = 0.014). CONCLUSION: Our study was unable to detect a difference in side effects using intermittent high-dose nitric-oxide inhalation or supportive treatment alone, in infants with moderate bronchiolitis. Preliminary efficacy outcomes are encouraging.


Subject(s)
Bronchiolitis/drug therapy , Nitric Oxide/therapeutic use , Administration, Inhalation , Bronchiolitis/blood , Double-Blind Method , Female , Hospitalization , Humans , Infant , Male , Methemoglobin/metabolism , Nitric Oxide/administration & dosage , Oxygen/metabolism , Pilot Projects , Respiratory Rate
16.
Proc Natl Acad Sci U S A ; 113(41): E6281-E6289, 2016 10 11.
Article in English | MEDLINE | ID: mdl-27671661

ABSTRACT

The basal ganglia (BG) network has been divided into interacting actor and critic components, modulating the probabilities of different state-action combinations through learning. Most models of learning and decision making in the BG focus on the roles of the striatum and its dopaminergic inputs, commonly overlooking the complexities and interactions of BG downstream nuclei. In this study, we aimed to reveal the learning-related activity of the external segment of the globus pallidus (GPe), a downstream structure whose computational role has remained relatively unexplored. Recording from monkeys engaged in a deterministic three-choice reversal learning task, we found that changes in GPe discharge rates predicted subsequent behavioral shifts on a trial-by-trial basis. Furthermore, the activity following the shift encoded whether it resulted in reward or not. The frequent changes in stimulus-outcome contingencies (i.e., reversals) allowed us to examine the learning-related neural activity and show that GPe discharge rates closely matched across-trial learning dynamics. Additionally, firing rates exhibited a linear decrease in sequences of correct responses, possibly reflecting a gradual shift from goal-directed execution to automaticity. Thus, modulations in GPe spiking activity are highest for attention-demanding aspects of behavior (i.e., switching choices) and decrease as attentional demands decline (i.e., as performance becomes automatic). These findings are contrasted with results from striatal tonically active neurons, which show none of these task-related modulations. Our results demonstrate that GPe, commonly studied in motor contexts, takes part in cognitive functions, in which movement plays a marginal role.


Subject(s)
Globus Pallidus/physiology , Learning/physiology , Action Potentials , Animals , Behavior, Animal , Chlorocebus aethiops , Corpus Striatum/physiology , Female , Neural Pathways , Reward
17.
Curr Opin Pediatr ; 27(3): 329-33, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25944313

ABSTRACT

PURPOSE OF REVIEW: To reflect the recent advances in the field of pediatric sleep medicine. The pediatrician will be able to define which children to refer for a sleep study and what to expect from the sleep specialist in 2015. RECENT FINDINGS: In the first study that compared adeno tonsillectomy (TA) to watchful waiting, TA reduced symptoms and improved children's behavior, quality of life, and polysomnographic results. Anti-inflammatory therapy for mild obstructive sleep apnea was effective and well tolerated according to a double-blind study. A retrospective study showed that it is beneficial for 80% of the patients. TA is associated with a decrease in asthma symptoms and medication utilization. SUMMARY: Pediatricians need to be aware of the clear benefits of tonsillectomy (including better asthma control), although anti-inflammatory therapy may improve symptoms and polysomnographic findings in children with nonsevere obstructive sleep apnea.


Subject(s)
Adenoidectomy , Polysomnography , Quality of Life , Sleep Apnea, Obstructive/surgery , Tonsillectomy , Watchful Waiting/methods , Child , Child Behavior , Child, Preschool , Double-Blind Method , Humans , Quality of Life/psychology , Retrospective Studies , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/psychology , Treatment Outcome
18.
Pediatr Pulmonol ; 50(2): 187-95, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24574078

ABSTRACT

BACKGROUND: Early life viral infection is associated with neurogenic inflammation that is present in lymphoid tissues of the upper airway in children with obstructive sleep apnea (OSA). We hypothesized that viral genomic material is present in tonsils of children with OSA. Therefore, we examined tonsils for the presence of respiratory viruses' nucleic acids in children with OSA, and in children without OSA (undergoing surgery for recurrent throat infections (RI)). METHODS: Tonsillar tissue from patients with OSA and RI was subjected to multiplex quantitative real time reverse transcription PCR (mqRTPCR), analyzed for the presence of common respiratory viruses' genetic material. RESULTS: Fifty-six patients were included, of whom 34 had OSA (age (years ± S.D), 4.22 ± 1.14) and 22 with RI (4.35 ± 1.36). Respiratory viruses nucleic acids (24 detections) were observed in 17 (50%) OSA samples. In contrast, no virus was detected in RI samples (relative frequency P<0.0001). Viruses detected, based on frequency were Rhinovirus, Adenovirus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), and corona virus. CONCLUSIONS: Respiratory viruses are detected in OSA hypertrophic tonsils, suggestive of their role in the evolution of tonsillar inflammation and hypertrophy. Early life viral infections may contribute to the pathogenesis of pediatric OSA.


Subject(s)
Palatine Tonsil/virology , Sleep Apnea, Obstructive/surgery , Child , Child, Preschool , DNA, Viral/genetics , Female , Humans , Hypertrophy , Male , Palatine Tonsil/pathology , Polymerase Chain Reaction , RNA, Viral/genetics , Tonsillectomy
19.
Mediators Inflamm ; 2014: 146893, 2014.
Article in English | MEDLINE | ID: mdl-25276051

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is associated with growth impairment that usually improves following effective treatment. In this study we investigated the mechanisms underlying the growth processes in young children diagnosed with OSA, before and after adenotonsillectomy (T&A). METHODS: Young children (6-36 months old) were enrolled and evaluated before and several months after T&A surgery for height, weight, circulating high sensitive C-reactive protein (CRP), and insulin-like growth factor 1 (IGF-1) levels. Caloric intake was assessed by a validated Short Food Frequency Questionnaire (SFFQ). RESULTS: Following T&A, children added 4.81 cm and 1.88 kg to their height and weight, respectively (P < 0.001 for both) and had a significant increase in BMI Z score (P = 0.002). Increased caloric intake of 377 kcal/day was noted (P < 0.001), with increased protein and decreased fat intake. The decrease in CRP levels correlated with the increase in body weight in boys (P < 0.05, adjusted for caloric intake). CONCLUSIONS: Adenotonsillectomy results in enhanced somatic growth in young children that correlates with a decrease in systemic inflammation and caloric intake increment. Our findings imply that systemic inflammation may have an important role in this OSA-related morbidity.


Subject(s)
Adenoidectomy , Sleep Apnea, Obstructive/immunology , Sleep Apnea, Obstructive/surgery , Tonsillectomy , C-Reactive Protein/metabolism , Child, Preschool , Female , Humans , Infant , Inflammation/immunology , Inflammation/metabolism , Male , Multivariate Analysis , Polysomnography , Sleep Apnea, Obstructive/metabolism , Surveys and Questionnaires , Treatment Outcome
20.
Sleep ; 36(12): 1947-55, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24293770

ABSTRACT

STUDY OBJECTIVES: Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS. DESIGN: Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1ß, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein). SETTING: Sleep research laboratory. PATIENTS OR PARTICIPANTS: Twenty-five children with OSAS and 24 without OSAS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1ß showed increased epithelial expression in OSAS tissues. CONCLUSIONS: Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.


Subject(s)
Inflammation/physiopathology , NF-kappa B/physiology , Sleep Apnea, Obstructive/physiopathology , Adenoids/physiology , C-Reactive Protein/analysis , Case-Control Studies , Child , Child, Preschool , Female , Humans , Interleukin-1alpha/physiology , Interleukin-1beta/physiology , Interleukin-8/physiology , Male , Palatine Tonsil/physiology , Tumor Necrosis Factor-alpha/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...