12 research outputs found
Studies of protein folding and misfolding on the ribosome
No full textProtein folding is one of the most important processes for maintaining cellular homeostasis. It begins co-translationally on the ribosome, however, it also competes with protein misfolding. Under severe conditions, protein misfolding can result in the accumulation of toxic aggregates, which are known to give rise to lethal conformational diseases including those linked to neurodegeneration, respiratory diseases, diabetes, and cancer. Very little is understood of co-translational protein misfolding mechanisms as they first begin in the cell, and also of their links to human disease. Alpha-1 deficiency, for example, results from pathological variants of the alpha-1-antitrypsin (AAT) protein, forming toxic polymer aggregates in the endoplasmic reticulum in hepatocytes, where the protein is synthesised.
To investigate aspects of co-translational misfolding, this Thesis examines the biosynthesis of AAT and of a pathological disease variant (Z AAT), on the ribosome, in a mammalian cell-free system, by applying quantitative biochemistry and structural biology techniques. These studies have revealed that ribosome-bound AAT nascent chains (NCs) form co-translational folding intermediates which are important for guiding correct folding (Chapter 3). Also observed are novel circumstances under which this process is hindered, as indicated by the presence of naturally-paused ribosomes at the full-length of AAT sequence; these induce ribosome collisions and the formation of higher-order ribosome-associated assemblies (Chapter 4), which are evident in biochemical assays and visualised using negative stain electron microscopy. The formation of ribosome-bound mis-assemblies, as investigated using sucrose density gradients and quantitative biochemistry, reveals that both “co-post” and “co-co” mechanisms are possible for the formation of AAT polymers (Chapter 5). Finally, a high-resolution cryo-EM structure of the AAT ribosome nascent chain complex (RNC), gives insights into the NC-ribosome interactions that could contribute to its natural stalling (Chapter 6).
A better understanding of the origins of the AAT toxic aggregates that lead to disease, will provide a foundation for therapeutics centred on early-intervention strategies
Investigation of parents’ knowledge focusing on children’s dermatological disorders regarding the use of biological versus chemicals products
No full textOBJECTIVEThe purpose of this study is to investigate the parents’ knowledge focusing on children’s dermatological disorders regarding the use of biological versus chemicals productsMETHODSThe current study took place from end of January 2014 to end of April 2014 in one pedo-dermatological and one pediatric in the Attica region.The study population was 200 children, 103 boys and 97 girls, age 0-5 years suffering from various types of dermatological disorders.The parents of each child completed a questionnaire assessing the clinical status of the child, the therapeutic approach adopted and the information concerning the economic and social approach of the patient's family.The data coding and the use of the statistical package IBM SPSS version 20 allowed the further configuration and statistical analysis of the findings.The appearance of dermatological disorders occurs in 50 % of the patients at the age of 0-7 months and in 50 % at the age of 8-60 months. The most frequent type of dermatitis in 80% of the patients was the atopic dermatitis. Symptoms of mild nature occurred in the majority of dermatitis. Atopic dermatitis reaches the largest percentage of acute and chronic dermatological disorders.The use of chemicals products like the corticosteroids is used to treat the symptoms of dermatitis. According to parents’ reply, the improvement based on the cortisone usage is valuable and at most considerable.Statistically significant correlation was found between the use of chemical products and the monthly cost of the treatment. Non chemical corticosteroids are mainly used as conservative - second line therapy. A percentage of 3.4 % of the patients presented an allergic reaction after the implementation of chemical corticosteroids and a rate of 27.3% showed irritation and itchiness after the application of non-chemical corticosteroids.The treatment of dermatitis, apart from the use of chemical products, is complemented with the use of other alternative methods, such as the use of biological products. 76.5 % of the patients seem to use biological products for topical use.A 40.10% of the sample suggested that biological products for topical use seams to have a considerable reduction on dermatitis exacerbation with their replies. There is also correlation between the use and the degree of biological products use with the level of parents’ awareness for biological products. Statistically significant correlation exists between the parents’ level of education with the use of biological products. No adverse reactions of biological products are recorded.CONCLUSIONBiological products for topical use seam to have a considerable reduction on dermatitis exacerbation.ΣΚΟΠΟΣΟ σκοπός της παρούσας μελέτης είναι η διερεύνηση των γνώσεων γονέων παιδιών με δερματοπάθειες για χρήση βιολογικών προϊόντων σε σύγκριση με χημικά προϊόντα.ΥΛΙΚΟ-ΜΕΘΟΔΟΣΗ παρούσα μελέτη πραγματοποιήθηκε το χρονικό διάστημα από τέλος Ιανουαρίου 2014 έως τέλος Απριλίου 2014 σε ένα παιδοδερματολογικό και ένα παιδιατρικό ιατρείο στην περιοχή της Αττικής.Τον μελετώμενο πληθυσμό αποτέλεσαν 200 παιδιά, 103 αγόρια και 97 κορίτσια, ηλικίας 0-5 ετών που έπασχαν από διάφορα είδη δερματοπάθειας. Συμπληρώθηκε ειδικό ερωτηματολόγιο από τους γονείς των ασθενών.Η συλλογή στοιχείων έγινε με τη συμπλήρωση ερωτηματολογίων.Η στατιστική επεξεργασία των στοιχείων έγινε με τη χρήση του στατιστικού πακέτου SPSS V.20.ΑΠΟΤΕΛΕΣΜΑΤΑΗ εμφάνιση της δερματοπάθειας παρουσιάζεται στο 50% των ασθενών σε ηλικία 0-7 μηνών και στο υπόλοιπο 50% σε ηλικία 8-60 μηνών. Ο πιο συχνός τύπος δερματίτιδας σε ποσοστό 80% ήταν η ατοπική δερματίτιδα. Όλες οι δερματοπάθειες στο μεγαλύτερο ποσοστό τους είναι ήπιας μορφής. Το μεγαλύτερο ποσοστό της οξείας αλλά και της χρόνιας δερματοπάθειας κατείχε η ατοπική δερματίτιδα.Η αντιμετώπιση των συμπτωμάτων της δερματοπάθειας γίνεται με τη χρήση χημικών σκευασμάτων,των κορτικοστεροειδών. Σύμφωνα με την εκτίμηση των γονέων, η βελτίωση που παρουσιάζεται στους ασθενείς κατά τη χρήση της κορτιζόνης είναι μεγάλη. Ένα ποσοστό 3,4% παρουσίασε αλλεργική αντίδραση μετά την εφαρμογή των χημικών κορτικοστεροειδών. Τα ανοσοτροποποιητικά χρησιμοποιούνται από το μεγαλύτερο ποσοστό των ασθενών ως θεραπεία συντήρησης. Ένα ποσοστό 27,3% παρουσίασε ερεθισμό και κνησμό μετά την εφαρμογή των χημικών μη κορτικοστεροειδών.Η αντιμετώπιση της δερματοπάθειας, πέραν της χρήσης των χημικών σκευασμάτων, γίνεται και με τη χρήση άλλων εναλλακτικών μεθόδων όπως η χρήση των βιολογικών προϊόντων. Οι ασθενείς του δείγματος δείχνουν να χρησιμοποιούν τα βιολογικά προϊόντα τοπικής χρήσης σε ποσοστό 76,5% και τα πόσιμα σε ποσοστό 18%. Από τη μελέτη προκύπτει ότι τα βιολογικά προϊόντα τοπικής χρήσης επιδρούν στη μείωση της έξαρσης της δερματοπάθειας. Το 40,10% των γονέων εκτιμάει ότι η χρήση των βιολογικών προϊόντων τοπικής χρήσης φαίνεται να μειώνει αρκετά την έξαρση των δερματοπαθειών.Υπάρχει επίσης στατιστικά σημαντική συσχέτιση μεταξύ της χρήσης και του βαθμού χρήσης των βιολογικών προϊόντων με τον βαθμό ενημέρωσης των γονέων για τα βιολογικά προϊόντα. Τέλος προκύπτει στατιστικά σημαντική συσχέτιση του επιπέδου εκπαίδευσης του γονέα με την χρήση βιολογικών προϊόντων. Ανεπιθύμητες ενέργειες των βιολογικών προϊόντων δεν καταγράφηκαν από τους γονείς των ασθενών του δείγματος.ΣΥΜΠΕΡΑΣΜΑΤΑΤα βιολογικά προϊόντα τοπικής χρήσης χρησιμοποιούνταν περισσότερο σε σύγκριση με τα πόσιμα βιολογικά προϊόντα. Τα βιολογικά προϊόντα τοπικής χρήσης επιδρούν στη μείωση της έξαρσης της δερματοπάθεια
Morbidity and outcomes of foreign travelers in Zakynthos island, Greece: a retrospective study.
No full textBACKGROUND: Although there is satisfactory recording of diseases affecting travelers visiting developing countries, little is known regarding morbidity of travelers when visiting developed countries. We sought to evaluate the morbidity of foreign travelers in Zakynthos, a popular Greek island attracting large number of foreign tourists every summer. METHODS: Data from foreign travelers that accommodated in Zakynthos and sought medical services from the private offices of Zante Medical Care from May 1 to October 30 2012 were retrospectively analyzed. RESULTS: Two thousand six hundred and eighty-eight patients were included in the study. The mean age (± SD) of the patients whom the age was recorded was 29.6 (± 18.3) and 51.5% of them were from 18 to 40 years old. Disorders of the respiratory tract (32.7%), dermatologic conditions (21.1%), musculoskeletal injuries (16.4%), and gastrointestinal disorders (16.3%) were the four most prevalent clinical categories among patients. Ear disorder was the most common syndromic description (14.5%) among which 81.2% were ear infections; otitis externa and otitis media were diagnosed in 8.5% and 3.3% patients in total. The most common specific diagnosis was gastroenteritis (14.3%). Insect bite and sunburn were the most common diagnosis (6.5% and 3.8%, respectively) among patients with a dermatologic condition. Ear infection was the most common diagnosis in pediatric patients. CONCLUSION: Disorders mainly of the upper respiratory tract were the predominant causes of illness among foreign travelers in Zakynthos. Traveler's diarrhea was the most common specific diagnosis but the prevalence within the total population was not very high
Morbidity of 2,688 patients by clinical category and most common specific diagnosis within each category.
No full text<p><b>Abbreviations</b></p><p>SD: standard deviation, y: year, F: female, UK: United Kingdom, SRB: Serbia, HU: Hungary, OR: odds ratio, CI: confidence interval.</p
Univariate and multivariate analyses regarding observation and need for hospitalization of 2,688 patients.
No full text<p><sup>*</sup> Data on age, gender, and duration of travel was not available for 92, 7, and 137 patients, respectively.</p><p><sup>**</sup> The remaining clinical categories are reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094416#pone-0094416-t002" target="_blank">Tables 2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094416#pone-0094416-t003" target="_blank">3</a>.</p><p><b>Abbreviations</b></p><p>y: year, F: female, d: day, UK: United Kingdom, SRB: Serbia, HU: Hungary, OR: odds ratio, CI: confidence interval.</p
Demographic characteristics of 2,688 patients.
No full text<p><sup>*</sup>Age was not recorded for 92 patients, while gender was not recorded for 7 patients.</p><p><sup>**</sup> The remaining travelers were from Italy (36), former Yugoslav Republic of Macedonia (30), Finland (29), Sweden (27), Slovenia (26), Ireland (24), Bulgaria (17), Austria (16), Belgium (10), Germany (10), Norway (10), Croatia (11), Switzerland (5), Slovakia (2), Lithuania (2), Australia (1), France (1), Ukraine (2), Brazil (1), Bosnia (1), while relevant data was not recorded from 5 travelers.</p><p><b>Abbreviations</b></p><p>SD: standard deviation, y: year, F: female, UK: United Kingdom, SRB: Serbia, HU: Hungary, OR: odds ratio, CI: confidence interval</p
Clinical Features, Risk Factors, and Complications Among Pediatric Patients With Pandemic Influenza A (H1N1)
No full text Objective. The authors aimed to describe the epidemiological characteristics, clinical features, risk factors for severe disease, and complications in children with laboratory-confirmed pandemic influenza A (H1N1). Methods. H1N1 was confirmed by performing reverse-transcriptase polymerase chain reaction (RT-PCR) assay on oropharyngeal swab specimens. The medical charts of a subset of the evaluated patients were reviewed retrospectively; another subset was enrolled prospectively. Results. A total of 51 patients (44 [86%] > 5 years) were identified to have laboratory-confirmed H1N1. Fever was the most common presenting symptom (92%). Of the 15 hospitalized patients, 4 had asthma, and 5 were overweight or obese. All but 1 of these 9 patients developed influenza-related complications. Overall, 10 of the 15 hospitalized patients (67%) developed an influenza-related complication (6 bronchitis and 4 pneumonia). Conclusion. In this cohort, most children with confirmed H1N1 infection experience an uncomplicated viral illness. Nevertheless, underlying asthma and obesity may aggravate their clinical course. </jats:p
Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis
No full textDeep venous thrombosis in children with musculoskeletal infections: the clinical evidence
No full textSummaryBackgroundClinical manifestations of deep venous thrombosis (DVT) tend to overlap with those of deep-seated musculoskeletal infections (MSIs). Consequently, the incidence of DVT as a complication of MSI may be underestimated. The objective of this study was to evaluate the incidence, clinical features, and outcomes of MSI-related DVT in children.MethodsWe systematically reviewed relevant studies retrieved from PubMed and Scopus databases.ResultsOverall, 93 children with MSIs who developed DVT were identified from 28 retrospective studies. The majority were boys. Osteomyelitis was the most frequent MSI (69/74, 93%). Staphylococcus aureus was the predominant pathogen (83/93, 89%); 61% of these isolates were methicillin-resistant S. aureus (MRSA). Pulmonary involvement, presumably due to septic emboli, was observed in 65% of the included children. Four children died due to multiple organ failure and two due to respiratory distress. In two of the three studies providing comparative data, MRSA infections were observed significantly more frequently in children who developed DVT compared to those who did not. Yet, the respective differences observed for methicillin-susceptible S. aureus (MSSA) infections were non-significant in these three studies.ConclusionsDespite the inclusion of many case reports and the retrospective design of the evaluated studies, our findings suggest that boys seem to be more frequently affected by MSIs complicated by DVT. Moreover, MRSA seems to be more frequently associated with DVT compared to MSSA. Pulmonary involvement appears to be a frequent complication. Prospective studies are needed in order to further clarify this issue
Morbidity and univariate analysis of 2,688 patients according to age, gender, month of travel, and duration of stay.
No full text<p><sup>*</sup> Data on age, gender, and duration of travel was not available for 92, 7, and 137 patients, respectively.</p><p><b>Abbreviations</b></p><p>y: year, F: female, M: male, d: day, UK: United Kingdom, SRB: Serbia, HU: Hungary, OR: odds ratio, CI: confidence interval, Aug: August, Sept: September, October.</p
