Short-chain Dehydrogenase/Reductase enzymes that are active on nucleotide sugars (abbreviated as NS-SDR) are of paramount importance in the biosynthesis of rare sugars and glycosides. Some family ...members have already been extensively characterized due to their direct implication in metabolic disorders or in the biosynthesis of virulence factors. In this review, we combine the knowledge gathered from studies that typically focused only on one NS-SDR activity with an in-depth analysis and overview of all of the different NS-SDR families (169,076 enzyme sequences). Through this structure-based multiple sequence alignment of NS-SDRs retrieved from public databases, we could identify clear patterns in conservation and correlation of crucial residues. Supported by this analysis, we suggest updating and extending the UDP-galactose 4-epimerase “hexagonal box model” to an “heptagonal box model” for all NS-SDR enzymes. This specificity model consists of seven conserved regions surrounding the NDP-sugar substrate that serve as fingerprint for each specificity. The specificity fingerprints highlighted in this review will be beneficial for functional annotation of the large group of NS-SDR enzymes and form a guide for future enzyme engineering efforts focused on the biosynthesis of rare and specialty carbohydrates.
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm characterized by mesenchymal spindle cell proliferation with a marked inflammatory infiltrate component. Although the exact etiopathology ...of pulmonary IMT is still not clear, gene fusions involving anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor (PDGFR) and rearranged during transfection (RET) have been recently detected in immunohistochemical assessment of this lesion. Due to its nonspecific clinical or radiological presentation, the diagnosis of IMT primarily depends on histopathological findings. Surgery remains the mainstay of treatment and provides the best chance to limit recurrence. In unresectable lesions or multifocal/metastatic disease, treatment with chemotherapy or ALK, ROS1, RET and NTRK inhibitors is recommended. The prognosis in children with IMT is generally perceived as favorable, although local invasion and metastasis have been reported.
Abstract Background An increasing incidence of parapneumonic effusion and pleural empyema (PPE/PE) in children has been found in several studies published in the last decades. The aim of the study ...was to evaluate the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. Material and methods We performed a retrospective analysis of clinical, radiological and laboratory data of all children aged between 1 month and 18 years with PPE/PE due to community acquired pneumonia (CAP) between January 2002 and December 2013. Results One thousand nine hundred and thirty three children with CAP were hospitalized between 2002 and 2013. Parapneumonic effusion or PE was diagnosed in 323 children (16.7%). The proportion of children with CAP related PPE/PE increased from 5.4% in 2002 to 18.8% in 2013. Streptococcus pneumoniae was the most common causative microorganism, responsible for 66.7% cases of known etiology. All children were treated with antibiotics and in 22.6%, and 74.3% of the patients therapeutic thoracentesis, pleural drainage with or without intrapleural fibrinolysis was performed, respectively. Approximately 3% of patients required surgical intervention. Conclusions A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the most common causative microorganism. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good.
Differences in treatment approach still exist for children after systemic sting reactions. In addition, there are still some doubts about when systemic reactors should be treated with venom ...immunotherapy (VIT).
To determine the rate of sting recurrence and natural history of Hymenoptera venom allergy (HVA) in children not treated with VIT.
A total of 219 children diagnosed as having HVA who were not treated with VIT were identified in 3 pediatric allergology centers. Survey by telephone or mail with the use of a standardized questionnaire was conducted. The number of field re-stings, subsequent symptoms, and provided treatment were analyzed.
A total of 130 of the 219 patients responded to the survey, for a response rate of 59.4%. During the median follow-up period of 72 months (interquartile range, 52-85 months), 44 children (77% boys) were stung 62 times. Normal reactions were most common, occurring in 27 patients (62%). Severe systemic reactions (SSRs) occurred in 8 (18%) of those who were re-stung. The subsequent reaction was significantly milder (P < 0.001), especially in the case of patients re-stung by the same insect (P < .001). None of the children with prediagnostic large local reactions and negative test results for venom specific IgE developed SSRs after re-sting by the culprit insect (P = .03). In children with SSRs, median time from diagnosis to re-sting was 2 times longer than that in those with large local reactions and normal reactions (P = .007).
Most children with HVA not treated with VIT reported milder reactions after a re-sting. Probability of SSR to re-sting increases along with the severity of initial reaction.
When Oleg Ptitsyn and his group published the first secondary structure prediction for a protein sequence, they started a research field that is still active today. Oleg Ptitsyn combined fundamental ...rules of physics with human understanding of protein structures. Most followers in this field, however, use machine learning methods and aim at the highest (average) percentage correctly predicted residues in a set of proteins that were not used to train the prediction method. We show that one single method is unlikely to predict the secondary structure of all protein sequences, with the exception, perhaps, of future deep learning methods based on very large neural networks, and we suggest that some concepts pioneered by Oleg Ptitsyn and his group in the 70s of the previous century likely are today's best way forward in the protein secondary structure prediction field.
Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome.
A retrospective, descriptive multicentre ...follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years.
Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0-12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function.
Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.
Background
Data on the prevalence and type of lung function impairment in preschool and school‐aged children previously diagnosed with persistent tachypnea of infancy (PTI) are scarce. Therefore, ...this study aims to assess pulmonary function in this age group.
Methods
Children diagnosed with PTI over 3 years old were admitted for follow‐up visits and healthy controls were enrolled. The study group included children who were able to complete pulmonary function tests (PFTs). Medical history, physical examination, and pulmonary function (spirometry, body plethysmography, impulse oscillometry, nitrogen multiple breath washout test, diffusing capacity for carbon monoxide DLCO) were assessed.
Results
Thirty‐seven children (26 boys, 11 girls; median age: 5.6 years) diagnosed with PTI and 37 healthy controls were recruited. Forced expiratory volume in 1 s and forced vital capacity were significantly lower (−1.12 vs. 0.48, p = 0.002 and −0.83 vs. 0.31, p = 0.009, respectively); respiratory resistance at 5 Hz (0.06 vs. −0.62, p = 0.003), resonant frequency (1.86 vs. 1.36, p = 0.04), residual volume (RV) (2.34 vs. −1.2, p < 0.0001), RV%TLC (total lung capacity) (2.63 vs. −0.72, p < 0.0001), and specific airway resistance (5.4 vs. 2.59, p = 0.04) were significantly higher in PTI patients as compared with controls (data were presented as median z‐score). Air trapping was found in 60.0%, and abnormally high lung clearance index and DLCO were found in 73.3% and 90.9% of PTI patients, respectively.
Conclusions
This study demonstrated that lung function is affected in most children with PTI. PFTs showed that peripheral airways are the major zone of functional impairment.
Unfortunately this article 1 was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below:
Funding
EAACI and the BM4SIT ...project (Grant Number 601763) in the European Union's Seventh Framework Programme FP7.
Intrinsically disordered proteins (IDPs) lack tertiary structure and thus differ from globular proteins in terms of their sequence-structure-function relations. IDPs have lower sequence conservation, ...different types of active sites and a different distribution of functionally important regions, which altogether make their multiple sequence alignment (MSA) difficult. The KMAD MSA software has been written specifically for the alignment and annotation of IDPs. It augments the substitution matrix with knowledge about post-translational modifications, functional domains and short linear motifs.
MSAs produced with KMAD describe well-conserved features among IDPs, tend to agree well with biological intuition, and are a good basis for designing new experiments to shed light on this large, understudied class of proteins.
KMAD web server is accessible at http://www.cmbi.ru.nl/kmad/ A standalone version is freely available.
vriend@cmbi.ru.nl.
Background
Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to ...treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)‐EU Register.
Methods
Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS.
Results
Thirty‐one children (median age: 44 months, interquartile range IQR: 15–67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p < 0.001), chest retractions (43.8% of patients, p = 0.04), and crackles (29.2% of patients, p = 0.02). Also, a significant improvement in forced expiratory volume in 1 s (FEV1) (median z score: −2.21 vs. −0.47, p = 0.03), residual volume (RV) (median z score 5.28 vs. 1.07, p = 0.007), RV% total lung capacity (TLC) (median z score: 6.05 vs. 1.48, p = 0.01), sRaw (median z score: 6.6 vs. 4.64, p = 0.01), R5 (median z score: 1.27 vs. 0.31, p = 0.009), and R5–R20 (median: 0.58 vs. 0.26 kPa/(l/s), p = 0.002) was demonstrated.
Conclusions
Inhaled bronchodilators and ICS may exert a positive effect on the severity of symptoms and pulmonary function test (PFT) in symptomatic children with PTI. However, a randomized control trial should be conducted to confirm their effectiveness.
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