Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial ...pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention.
A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases.
This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine.
Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.
Adolescents may not receive the sleep they need. New media technology and new, popular energy drinks may be implicated in sleep deficits. In this pilot study we quantified nighttime technology use ...and caffeine consumption to determine effects on sleep duration and daytime behaviors in adolescents. We hypothesized that with increased technology use, adolescents increase caffeine consumption, resulting in insufficient sleep duration.
Subjects were recruited from a pediatric office in a proximal suburb of Philadelphia, Pennsylvania. Inclusion criteria for this study were middle and high school subjects aged 12 to 18 years old. The questionnaire, Adolescent Sleep, Caffeine Intake, and Technology Use, was developed by the investigators to measure adolescents' intake of caffeinated drinks, use of nighttime media-related technology, and sleep behaviors. Descriptive statistics characterized the subjects, their caffeine and technology use, and sleep variables. Regression models assessed the relationships between caffeine, technology use, and sleep variables, having adjusted for age, race, gender, and BMI.
Sleep was significantly related to the multitasking index. Teenagers getting 8 to 10 hours of sleep on school nights tended to have 1.5- to 2-fold lower multitasking indices compared with those getting less sleep. Thirty-three percent of the teenagers reported falling asleep during school. Caffeine consumption tended to be 76% higher by those who fell asleep. The log-transformed multitasking index was significantly related to falling asleep during school and with difficulties falling asleep on weeknights.
Many adolescents used multiple forms of technology late into the night and concurrently consumed caffeinated beverages. Subsequently, their ability to stay alert and fully functional throughout the day was impaired by excessive daytime sleepiness. Future studies should measure more than television hours when evaluating the impact of nighttime activities on sleep patterns in adolescents.
The morphodynamic response of the nearshore zone of an embayed beach induced by wave groups is examined with a numerical model. The model utilizes the nonlinear shallow water equations to phase ...resolve the mean and infragravity motions in combination with an advection‐diffusion equation for the sediment transport. The sediment transport associated with the short‐wave asymmetry is accounted for by means of a time‐integrated contribution of the wave nonlinearity using stream function theory. The two‐dimensional (2‐D) computations consider wave group energy made up of directionally spread, short waves with a zero mean approach angle with respect to the shore normal, incident on an initially alongshore uniform barred beach. Prior to the 2‐D computations, the model is calibrated with prototype flume measurements of waves, currents, and bed level changes during erosive and accretive conditions. The most prominent feature of the 2‐D model computations is the development of an alongshore quasi‐periodic bathymetry of shoals cut by rip channels. Without directional spreading, the smallest alongshore separation of the rip channels is obtained, and the beach response is self‐organizing in nature. Introducing a small amount of directional spreading (less than 2°) results in a strong increase in the alongshore length scales as the beach response changes from self‐organizing to being quasi‐forced. A further increase in directional spreading leads again to smaller length scales. The hypothesized correlation between the observed rip spacing and wave group forced edge waves over the initially alongshore uniform bathymetry is not found. However, there is a correlation between the alongshore length scales of the wave group‐induced quasi‐steady flow circulations and the eventual alongshore spacing of the rip channels. This suggests that the scouring associated with the quasi‐steady flow induced by the initial wave groups triggers the development of rip channels via a positive feedback mechanism in which the small scour holes start attracting more and more discharge.
A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most ...common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion‐transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P‐glycoprotein (P‐gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst‐case scenario for P‐gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions.
Despite the known biochemical production of a range of aromatic compounds by plants and the presence of benzenoids in floral scents, the emissions of only a few benzenoid compounds have been reported ...from the biosphere to the atmosphere. Here, using evidence from measurements at aircraft, ecosystem, tree, branch and leaf scales, with complementary isotopic labeling experiments, we show that vegetation (leaves, flowers, and phytoplankton) emits a wide variety of benzenoid compounds to the atmosphere at substantial rates. Controlled environment experiments show that plants are able to alter their metabolism to produce and release many benzenoids under stress conditions. The functions of these compounds remain unclear but may be related to chemical communication and protection against stress. We estimate the total global secondary organic aerosol potential from biogenic benzenoids to be similar to that from anthropogenic benzenoids (~10 Tg y(-1)), pointing to the importance of these natural emissions in atmospheric physics and chemistry.
Objective:
To determine pre- and postoperative prevalence of obstructive sleep apnea (OSA) in patients with 22q11.2 deletion syndrome (DS) undergoing wide posterior pharyngeal flap (PPF) surgery for ...velopharyngeal dysfunction (VPD).
Design:
Retrospective study using pre- and postoperative polysomnography (PSG) to determine prevalence of OSA. Medical records were reviewed for patients’ medical comorbidities. Parents were surveyed about snoring.
Setting:
Academic tertiary care pediatric hospital.
Patients:
Forty patients with laboratory confirmed 22q11.2DS followed over a 6-year period.
Interventions:
Pre- and postoperative PSG, speech evaluation, and parent surveys.
Main Outcome Measure:
Severity and prevalence of OSA, defined by obstructive apnea hypopnea index (OAHI), before and after PPF surgery to determine whether PPF is associated with increased risk of OSA.
Results:
Mean OAHI did not change significantly after PPF surgery (1.1/h vs 2.1/h, P = .330). Prevalence of clinically significant OSA (OAHI ≥ 5) was identical pre- and postoperatively (2 of 40), with both cases having severe-range OSA requiring positive airway pressure therapy. All other patients had mild-range OSA. Nasal resonance was graded as severe preoperatively in 85% of patients. None were graded as severe postoperatively. No single patient factor or parent-reported concern predicted risk of OSA (OAHI ≥ 1.5).
Conclusions:
Patients with 22q11.2DS are medically complex and are at increased risk of OSA at baseline. Wide PPF surgery for severe VPD does not significantly increase risk of OSA. Careful perioperative planning is essential to optimize both speech and sleep outcomes.
TDP-43 is a nuclear protein involved in exon skipping and alternative splicing. Recently, TDP-43 has been identified as the pathological signature protein in frontotemporal lobar degeneration with ...ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. In addition, TDP-43-positive inclusions are present in Parkinson disease, dementia with Lewy bodies, and 30% of Alzheimer disease cases. Pathological TDP-43 is redistributed from the nucleus to the cytoplasm, where it accumulates. An ∼25-kDa C-terminal fragment of TDP-43 accumulates in affected brain regions, suggesting that it may be involved in the disease pathogenesis. Here, we show that overexpression of the 25-kDa C-terminal fragment is sufficient to cause the mislocalization and cytoplasmic accumulation of endogenous full-length TDP-43 in two different cell lines, thus recapitulating a key biochemical characteristic of TDP-43 proteinopathies. We also found that TDP-43 mislocalization is associated with a reduction in the low molecular mass neurofilament mRNA levels. Notably, we show that the autophagic system plays a role in TDP-43 metabolism. Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. Our results suggest that autophagy induction may be a valid therapeutic target for TDP-43 proteinopathies.
Pediatric parasomnias MASON, Thornton B. A; PACK, Allan I
Sleep (New York, N.Y.),
02/2007, Letnik:
30, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Parasomnias in childhood are common, and often more frequent than in adults. The large number of parasomnias underscore that sleep is not simply a quiescent state, but can involve complex episodes of ...movement, ranging from subtle to dramatic and complex. Clinicians should be aware that many pediatric parasomnias are benign, self-limited, and may not persist into late childhood or adolescence. Importantly, parasomnias in childhood often differ in type from adults. Nevertheless, parasomnias across ages can be classified as: 1) disorders of arousal (from non-rapid eye movement, or NREM, sleep); 2) parasomnias usually associated with REM sleep; and 3) other parasomnias. We detail here issues in the clinical diagosis, evaluation, and management of multiple pediatric parasomnias. The further study of parasomnias in children may help elucidate the multi-factorial etiologies of these fascinating conditions, shedding light on the potential genetic bases as well as environmental contributions.
Inflammation of the middle ear, known clinically as chronic otitis media, presents in different forms, such as chronic otitis media with effusion (COME; glue ear) and chronic suppurative otitis media ...(CSOM). These are highly prevalent diseases, especially in childhood, and lead to significant morbidity worldwide. However, much remains unclear about this disease, including its aetiology, initiation and perpetuation, and the relative roles of mucosal and leukocyte biology, pathogens, and Eustachian tube function. Chronic otitis media is commonly modelled in mice but most existing models only partially mimic human disease and many are syndromic. Nevertheless, these models have provided insights into potential disease mechanisms, and have implicated altered immune signalling, mucociliary function and Eustachian tube function as potential predisposing mechanisms. Clinical studies of chronic otitis media have yet to implicate a particular molecular pathway or mechanism, and current human genetic studies are underpowered. We also do not fully understand how existing interventions, such as tympanic membrane repair, work, nor how chronic otitis media spontaneously resolves. This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition. It also identifies unanswered questions about its pathogenesis and treatment, with the goal of advancing our understanding of this disease to aid the development of novel therapeutic interventions.
The biosphere is the major source and sink of nonmethane volatile organic compounds (VOCs) in the atmosphere. Gas-phase chemical reactions initiate the removal of these compounds from the atmosphere, ...which ultimately proceeds via deposition at the surface or direct oxidation to carbon monoxide or carbon dioxide. We performed ecosystem-scale flux measurements that show that the removal of oxygenated VOC via dry deposition is substantially larger than is currently assumed for deciduous ecosystems. Laboratory experiments indicate efficient enzymatic conversion and potential up-regulation of various stress-related genes, leading to enhanced uptake rates as a response to ozone and methyl vinyl ketone exposure or mechanical wounding. A revised scheme for the uptake of oxygenated VOCs, incorporated into a global chemistry-transport model, predicts appreciable regional changes in annual dry deposition fluxes.
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