Prevention and the treatment of oral mucositis: the efficacy of sodium bicarbonate vs other agents: a systematic review.

INTRODUCTION: Oral mucositis (OM) is a major side effect of cancer therapy, which is associated with significant symptoms, treatment delays and increased costs for the health system. It is an important component of the quality of life of cancer patients and, until now, there has been no gold standard regarding prevention or treatment of this pathology. Notwithstanding the paucity of treatment guidelines (due to limited evidence from high-quality, rigorous studies), sodium bicarbonate (SB) rinses are one of the most used agents for OM management. OBJECTIVES: A systematic review (2000-2022) was performed in order to compare and examine different agents versus sodium bicarbonate (SB) in preventing or treating OM. SOURCES: Eleven randomized controlled trials (RCT) were evaluated: four were conducted for the prevention and seven for the management of OM. The risk of bias of RCTs was assessed using the revised Cochrane risk of bias tool for randomized trials. STUDY SELECTION: According to the RoB2 evaluation for randomized trials, four RCTs were judged to be at a high risk of bias, two were rated as 'problematic', while five were deemed to be a low risk of bias. CONCLUSIONS: The results revealed that there was no evidence for supporting SB in OM treatment regarding management and prevention. CLINICAL SIGNIFICANCE: Results showed in this review takes on a strategic importance in the use of SB for OM management or prevention; indiscriminate use of SB could be counterproductive because it causes a sudden pH increase and it delays proper OM pharmacological treatment.

Mechanism based therapies enable personalised treatment of hypertrophic cardiomyopathy.

Cardiomyopathies have unresolved genotype-phenotype relationships and lack disease-specific treatments. Here we provide a framework to identify genotype-specific pathomechanisms and therapeutic targets to accelerate the development of precision medicine. We use human cardiac electromechanical in-silico modelling and simulation which we validate with experimental hiPSC-CM data and modelling in combination with clinical biomarkers. We select hypertrophic cardiomyopathy as a challenge for this approach and study genetic variations that mutate proteins of the thick (MYH7R403Q/+) and thin filaments (TNNT2R92Q/+, TNNI3R21C/+) of the cardiac sarcomere. Using in-silico techniques we show that the destabilisation of myosin super relaxation observed in hiPSC-CMs drives disease in virtual cells and ventricles carrying the MYH7R403Q/+ variant, and that secondary effects on thin filament activation are necessary to precipitate slowed relaxation of the cell and diastolic insufficiency in the chamber. In-silico modelling shows that Mavacamten corrects the MYH7R403Q/+ phenotype in agreement with hiPSC-CM experiments. Our in-silico model predicts that the thin filament variants TNNT2R92Q/+ and TNNI3R21C/+ display altered calcium regulation as central pathomechanism, for which Mavacamten provides incomplete salvage, which we have corroborated in TNNT2R92Q/+ and TNNI3R21C/+ hiPSC-CMs. We define the ideal characteristics of a novel thin filament-targeting compound and show its efficacy in-silico. We demonstrate that hybrid human-based hiPSC-CM and in-silico studies accelerate pathomechanism discovery and classification testing, improving clinical interpretation of genetic variants, and directing rational therapeutic targeting and design.

A 77-Year-Old Woman With Capillary Hypoxia and Perioral Cyanosis.

CASE PRESENTATION: A 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Spo2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia.

Consumer attitudes towards farm animal welfare in Argentina, Chile, Colombia, Ecuador, Peru and Bolivia: A segmentation-based study.

Consumer attitudes towards farm animal welfare (FAW) are not a one-dimensional phenomenon; they entail various attitudinal and social dimensions related to ethnicity, agri-food culture, ethics, purchasing power and beliefs. Therefore, the study aimed to identify segments of South American consumers of animal products according to their attitudes towards FAW. An online survey was carried out among participants from Argentina, Chile, Colombia, Ecuador, Peru and Bolivia (n = 2852). A factor analysis followed by a hierarchical cluster analysis identified four consumers' segments based on their attitudes towards FAW. The first corresponds to consumers ethically committed to FAW (n = 1323), the second to those committed to farmers and interested in labels (n = 215), the third to consumers interested in FAW and farmers and their efforts towards FAW (n = 993), and the fourth, associated with apathetic consumers (n = 321). Although FAW is a relatively new commercial phenomenon in South America, our results showed that concern for animals may be a universal human value, which can overcome traditional dichotomies between rich-poor or developed-undeveloped countries.

Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts' cardiac electrical and mechanical functions. However, the durability of effect, immune response, and in vitro properties of the tissue graft remained uncharacterized. This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft. METHODS: hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. RESULTS: The epicardially placed tissue graft therapy improved (p < 0.05) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles. CONCLUSIONS: This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option.

CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes.

[Figure: see text].

Discordant clinical features of identical hypertrophic cardiomyopathy twins.

Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or environmental factors drive these differences, we studied disease progression in 11 pairs of monozygotic HCM twins. The twin pairs were followed for 5 to 14 y, and left ventricular wall thickness, left atrial diameter, and left ventricular ejection fraction were collected from echocardiograms at various time points. All nine twin pairs with sarcomere protein gene variants and two with unknown disease etiologies had discordant morphologic features of the heart, demonstrating the influence of nonhereditable factors on clinical expression of HCM. Whole genome sequencing analysis of the six monozygotic twins with discordant HCM phenotypes did not reveal notable somatic genetic variants that might explain their clinical differences. Discordant cardiac morphology of identical twins highlights a significant role for epigenetics and environment in HCM disease progression.

Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in TNNI3 and TNNT2 That Are Common in Chinese Patients.

BACKGROUND: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry. METHODS: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies. RESULTS: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P<0.0001) but an excess of variants of uncertain significance (24%, P<0.0001), as compared to Whites (pathogenic/likely pathogenic: 31%, excess of variants of uncertain significance: 7%). Two missense variants in thin filament encoding genes were commonly seen in Singaporean HCM (TNNI3:p.R79C, disease allele frequency [AF]=0.018; TNNT2:p.R286H, disease AF=0.022) and are enriched in Singaporean HCM when compared with Asian controls (TNNI3:p.R79C, Singaporean controls AF=0.0055, P=0.0057, genome aggregation database-East Asian AF=0.0062, P=0.0086; TNNT2:p.R286H, Singaporean controls AF=0.0017, P<0.0001, genome aggregation database-East Asian AF=0.0009, P<0.0001). Both these variants have conflicting annotations in ClinVar and are of low penetrance (TNNI3:p.R79C, 0.7%; TNNT2:p.R286H, 2.7%) but are predicted to be deleterious by computational tools. In population controls, TNNI3:p.R79C carriers had significantly thicker left ventricular walls compared with noncarriers while its etiological fraction is limited (0.70 [95% CI, 0.35-0.86]) and thus TNNI3:p.R79C is considered variant of uncertain significance. Mutant TNNT2:p.R286H iPSC-CMs (induced pluripotent stem cells derived cardiomyocytes) show hypercontractility, increased metabolic requirements, and cellular hypertrophy and the etiological fraction (0.93 [95% CI, 0.83-0.97]) support the likely pathogenicity of TNNT2:p.R286H. CONCLUSIONS: As compared with Whites, Chinese HCM patients commonly have low penetrance risk alleles in TNNT2 or TNNI3 but exhibit few clinically actionable HCM variants overall. This highlights the need for greater study of HCM genetics in non-White populations.

Antimicrobial photodynamic therapy mediated by methylene blue in surfactant vehicle on periodontopathogens.

BACKGROUND: Periodontal disease (PD) is a chronic inflammatory disease caused by the presence of microbial biofilm. The aim of this study was to evaluate antimicrobial effect of antimicrobial photodynamic therapy (A-PDT) mediated by methylene blue (MB) in monomer form on A. actinomycetemcomitans and P. gingivalis. METHODS: A. actinomycetemcomitans ATCC 29523 and P. gingivalis ATCC 33577 were cultured on anaerobic jars at 37 °C for 48 h, and we tested APDT in the presence of 0.25% sodium dodecyl sulfate (SDS) in phosphate-buffered saline (PBS) or in PBS alone. APDT was carried out with 100 µM MB under laser radiation (PhotolaseIII, DMC, Brazil) at ʎ =660 nm and parameters as following (P =100 mW; I =250 mW/cm2, and doses of 15, 45 and 75 J/cm2). RESULTS: Following A-PDT, PBS groups of A. actinomycetemcomitans presented 4 Logs of microbial death after 5 min irradiation. However, there was no bacterial reduction in SDS groups. On the other hand, P. gingivalis was sensitive to APDT in the presence of 0.25% SDS with 2 logs reduction from dark toxicity. CONCLUSION: The presence of 0.25% SDS can lead to different responses depending on the different microbial species.

Novel Therapies for Prevention and Early Treatment of Cardiomyopathies.

Heritable cardiomyopathies are a class of heart diseases caused by variations in a number of genetic loci. Genetic variants on one allele lead to either a degraded protein, which causes a haploinsufficiency of that protein, or a nonfunctioning protein that subverts the molecular system within which the protein works. Over years, both of these mechanisms eventually lead to diseased heart tissue and symptoms of a failing heart. Most cardiomyopathy treatments repurpose heart failure drugs to manage these symptoms and avoid adverse outcomes. There are few therapies that correct the underlying pathogenic genetic or molecular mechanism. This review will reflect on this unmet clinical need in genetic cardiomyopathies and consider a variety of therapies that address the mechanism of disease rather than patient symptoms. These therapies are genetic, targeting a defective gene or transcript, or ameliorating a genetic insufficiency. However, there are also a number of small molecules under exploration that modulate downstream faulty protein products affected in cardiomyopathies.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch in Rats With Heart Failure.

BACKGROUND: To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. METHODS: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n = 12) or left coronary artery ligation (n = 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. RESULTS: Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), ß-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. CONCLUSIONS: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.

Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity.

Amblyomin-X, a Kunitz-type protease inhibitor, is a recombinant protein that selectively induces apoptosis in tumor cells and promotes tumor reduction in vivo in melanoma animal models. Furthermore, Amblyomin-X was able to drastically reduce lung metastasis in a mice orthotopic kidney tumor model. Due to its antitumor activity, Amblyomin-X potential to become a new drug is currently under investigation, therefore the aim of the present study was to perform preclinical assays to evaluate Amblyomin-X toxicity in healthy mice. Exploratory toxicity assays have shown that treatment with 512 mg/kg of Amblyomin-X lead to animal mortality, therefore two groups of treatment were evaluated in the present work: in the acute toxicity assay, animals were injected once with doses ranging from 4 to 256 mg/kg of Amblyomin-X, while in the subacute toxicity assay, animals were injected with 0.25, 0.57 and 1 mg/kg of Amblyomin-X daily, during 28 days. Following this treatment regimens, Amblyomin-X did not cause any mortality; moreover, toxicity signs were discrete, reversible and observed only at the higher doses, thus establishing a safety profile for administration in mice, which can be further used to determine the dose translation of this novel drug candidate for treatment in other species.

Feature Selection and Comparison of Machine Learning Algorithms in Classification of Grazing and Rumination Behaviour in Sheep.

Grazing and ruminating are the most important behaviours for ruminants, as they spend most of their daily time budget performing these. Continuous surveillance of eating behaviour is an important means for monitoring ruminant health, productivity and welfare. However, surveillance performed by human operators is prone to human variance, time-consuming and costly, especially on animals kept at pasture or free-ranging. The use of sensors to automatically acquire data, and software to classify and identify behaviours, offers significant potential in addressing such issues. In this work, data collected from sheep by means of an accelerometer/gyroscope sensor attached to the ear and collar, sampled at 16 Hz, were used to develop classifiers for grazing and ruminating behaviour using various machine learning algorithms: random forest (RF), support vector machine (SVM), k nearest neighbour (kNN) and adaptive boosting (Adaboost). Multiple features extracted from the signals were ranked on their importance for classification. Several performance indicators were considered when comparing classifiers as a function of algorithm used, sensor localisation and number of used features. Random forest yielded the highest overall accuracies: 92% for collar and 91% for ear. Gyroscope-based features were shown to have the greatest relative importance for eating behaviours. The optimum number of feature characteristics to be incorporated into the model was 39, from both ear and collar data. The findings suggest that one can successfully classify eating behaviours in sheep with very high accuracy; this could be used to develop a device for automatic monitoring of feed intake in the sheep sector to monitor health and welfare.

Effect of claw horn lesion type and severity at the time of treatment on outcome of lameness in dairy cows.

Prompt diagnosis and treatment of claw horn lesions in cattle affects the likelihood of recovery; however, it is unknown if the type of lesion influences the likelihood of recovery. The aim of this study was to investigate whether the type, severity and frequency of claw horn lesions in newly lame cows (lame for no more than 2 weeks) at the time of corrective foot trimming affects the probability of recovery from lameness after treatment. The images of 112 feet (224 claws) from newly lame cows (n=112; lame in only one hind foot), which were treated with a standardised therapeutic hoof trim only, were used to score claw horn lesions (sole ulcer, sole haemorrhage, white line haemorrhage or white line separation). Most cows (n=107/112; 95.5%) were classified as mildly lame at the time of treatment. The proportion of cows that recovered 2 weeks after therapeutic hoof trimming was 88/112 (78.6%). Results of a multilevel logistic regression model indicated that severely lame cows were less likely to recover than those that were mildly lame (odds ratio, OR, 0.16; P=0.04). White line haemorrhage had a significant negative impact on the likelihood of recovery from lameness (OR 0.14; P>0.01); however, recovery of cows with white line haemorrhage was positively associated with the length of the lesion (OR 1.05; P=0.03). This latter finding may be associated with the severity of the lesion, since mild claw horn lesions affected a significantly larger area of the claw than more severe lesions. The length and type of claw horn lesion were associated with recovery from lameness.

Large-Scale Production of Mature Neurons from Human Pluripotent Stem Cells in a Three-Dimensional Suspension Culture System.

Human pluripotent stem cells (hPSCs) offer a renewable source of cells that can be expanded indefinitely and differentiated into virtually any type of cell in the human body, including neurons. This opens up unprecedented possibilities to study neuronal cell and developmental biology and cellular pathology of the nervous system, provides a platform for the screening of chemical libraries that affect these processes, and offers a potential source of transplantable cells for regenerative approaches to neurological disease. However, defining protocols that permit a large number and high yield of neurons has proved difficult. We present differentiation protocols for the generation of distinct subtypes of neurons in a highly reproducible manner, with minimal experiment-to-experiment variation. These neurons form synapses with neighboring cells, exhibit spontaneous electrical activity, and respond appropriately to depolarization. hPSC-derived neurons exhibit a high degree of maturation and survive in culture for up to 4-5 months, even without astrocyte feeder layers.

Reciprocated cross sucking between dairy calves after weaning off milk does not appear to negatively affect udder health or production.

Cross sucking by dairy calves occurs most commonly before weaning, but is of most concern in older animals where it has been claimed to cause mastitis and udder damage. Providing ad libitum milk allowance via a teat and gradual weaning reduces cross sucking, but low levels of this behavior still persist. Our aims were to understand why this behavior persists in some calves after weaning off milk and to examine whether individuals which are cross sucked postweaning are more likely to sustain teat injury or develop mastitis during their first lactation. Fifty-six female Holstein calves were housed in groups of 8 and fed milk, grain, and hay ad libitum from automated feeders. During weaning, milk allowance was gradually reduced according to grain intake. Cross sucking was recorded using overhead video cameras (5 observation periods of 72h). The effects of weaning on cross sucking were examined; to examine whether cross sucking affected udder health, all incidences of damaged quarters or clinical and sub-clinical mastitis in the first lactation were recorded, as was milk production. The overall level of cross sucking after weaning, at 4 to 5mo of age, was low and a small proportion of individuals accounted for the majority of events. The duration of cross sucking that occurred at 4 to 5mo of age was correlated with the amount of cross sucking done before and immediately after weaning. After weaning, the calves that cross sucked did so on certain calves, with the most sucked calf within each pen accounting for 73.98% of all cross-sucking events. No relationship was found between cross sucking and being cross sucked in the period before weaning but a positive correlation was found by 4 to 5mo of age. The majority of calves reduced or ceased cross sucking after weaning. Individuals still observed to be cross sucking by 4 to 5mo of age had formed pairs with other cross-sucking individuals and cross-sucking events occurred almost exclusively between these pairs. Cows that were cross sucked as heifers were no more likely to develop mastitis or have higher somatic cell count in their first lactation than those which were not involved in cross sucking. Cross sucking typically begins before weaning, but the formation of lasting pairs of reciprocal cross-sucking partners after weaning may be responsible for this behavior persisting in group housed dairy calves after weaning off milk. Low levels of cross sucking did not appear to have a negative effect on udder health.

Barriers to Receiving Follow-Up Eye Care and Detection of Non-Glaucomatous Ocular Pathology in the Philadelphia Glaucoma Detection and Treatment Project.

This cross-sectional study aimed to evaluate adherence rates and identify barriers to receiving follow-up eye care in participants diagnosed with significant non-glaucomatous eye pathology in the Philadelphia Glaucoma Detection and Treatment Project. This community-based project aimed to improve detection, management, treatment, and follow-up eye care of individuals at high risk for glaucoma in community-based settings. Participants throughout Philadelphia, Pennsylvania, USA were enrolled. After a comprehensive eye examination, follow-up recommendations were given to each participant. A telephone survey was administered to individuals diagnosed with non-glaucomatous ocular pathology 3 months after initial eye examination to assess rates of follow-up and to evaluate potential barriers to follow-up. Of the 1649 participants enrolled in this project, 249 (15 %) were diagnosed with significant non-glaucomatous ocular pathology requiring follow-up care. There were 143 (57 %) who responded to the telephone survey. Respondents had a median age of 72 years, and were predominately female (69 %) and African-American (64 %). Of the respondents, 36 (25 %) attended a follow-up appointment. Participants who did not remember the results of their examinations, did not remember their recommendations, and had not seen an eye doctor within the past year were less likely to make a follow-up appointment (P = 0.04, 0.001 and 0.005, respectively). The Philadelphia Glaucoma Detection and Treatment Program was able to detect a significant amount of non-glaucomatous ocular pathology requiring follow-up care. Actual follow-up rates were sub-optimal. Further research is needed to determine interventions to overcome barriers and increase adherence with follow-up recommendations.

Healthy environment--indoor air quality of Brazilian elementary schools nearby petrochemical industry.

The mitigation of pollution released to the environment originating from the industrial sector has been the aim of all policy-makers and its importance is evident if the adverse health effects on the world population are considered. Although this concern is controversial, petroleum refinery has been linked to some adverse health effects for people living nearby. Apart from home, school is the most important indoor environment for children and there is increasing concern about the school environment and its impact on health, also in developing countries where the prevalence of pollution is higher. As most of the children spend more than 40% of their time in schools, it is critical to evaluate the pollution level in such environment. In the metropolitan region of Curitiba, South Brazil, five schools nearby industries and highways with high density traffic, were selected to characterize the aerosol and gaseous compounds indoor and outdoor of the classrooms, during 2009-2011. Size segregated aerosol samples were collected for analyses of bulk and single particle elemental profiles. They were analyzed by electron probe X-ray micro-analysis (EPXMA), and by energy-dispersive X-ray fluorescence (EDXRF), to investigate the elemental composition of individual particles and bulk samples. The concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX); NO2; SO2; acetic acid; and formic acid were assessed indoor and outdoor using passive diffusion tubes. BTEX were analyzed by GC-MS and other collected gasses by ion chromatography. Individual exposition of BTEX was assessed by personal passive diffusion tubes. Results are interpreted separately and as a whole with the specific aim of identifying compounds that could affect the health of the scholars. In view of the chemical composition and size distribution of the aerosol particles, local deposition efficiencies in the children's respiratory systems were calculated, revealing the deposition of particles at extrathoracic, tracheobronchial and pulmonary levels.