A THz transparent 3D printed microfluidic cell for small angle x-ray scattering.

Excitation frequencies in the terahertz (THz) range are expected to lead to functionally relevant domain movements within the biological macromolecules such as proteins. The possibility of examining such movements in an aqueous environment is particularly valuable since here proteins are not deprived of any motional degrees of freedom. Small angle x-ray scattering (SAXS) is a powerful method to study the structure and domain movements of proteins in solution. Here, we present a microfluidic cell for SAXS experiments, which is also transparent for THz radiation. Specifically, cell dimensions and material were optimized for both radiation sources. In addition, the polystyrene cell can be 3D printed and easily assembled. We demonstrate the practicality of our design for SAXS measurements on several proteins in solution.

Structural phase transformations in annealed Pt/Mn/Fe trilayers.

Thermally-activated phase transitions in Pt/Mn/Fe thin films were investigated by a combination of x-ray diffraction, transmission electron microscopy, secondary neutral mass spectrometry depth profiling, atomic force microscopy, and magnetic properties measurements. Post-annealing was carried out in vacuum to different temperatures up to 620 °C. Initially, at temperatures between 280 °C-450 °C first L10-MnPt is formed at the Mn/Pt interface followed by the most likely formation of metastable bcc Fe3Pt, which gets transformed by further annealing to fcc Fe3Pt and eventually to chemically ordered L12-Fe3Pt. The final product after annealing at 620 °C consists of two interesting phases, which are relevant for spintronic applications, antiferromagnetic L10-MnPt with addition of Fe and ferromagnetic L12-Fe3Pt, consistent with the initial element composition.

In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors.

Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

Phase transformations in Pt/Fe bilayers during post annealing probed by resistometry.

X-ray diffraction (XRD), secondary neutral mass spectrometry (SNMS) depth profiling, and electrical resistivity measurements were used to follow the phase transformations in Pt/Fe bi-layered thin films during annealing. Initially, the electrical resistivity increases linearly with temperature up to 150 °C due to the contribution of phonon scattering of the metallic Pt and Fe bilayer. Further increase of the annealing temperature leads to a steeper linear increase, which is associated with the initial formation of the chemically disordered A1-phase followed by the formation of the chemically ordered L10-FePt phase, as confirmed by XRD and SNMS studies. Finally, at about 620 °C the single L10-FePt phase has formed throughout the film. Moreover, the electrical resistivity contains also the magnetic contribution to the total resistivity. In this case, the loss in magnetic order is indicated by a change in temperature dependence of the resistivity at about 310 °C, representing the Curie temperature of the initially formed A1-FePt alloy, while the finally formed L10-FePt alloy reveals a higher magnetic transition temperature of about 410 °C. In this study, it has been demonstrated that resistometry in combination with structural and chemical analysis provides valuable information on diffusion processes, structural phase formations and its stability range, as well as on the magnetic transition temperature.

Trends in prevalence and risk factors of allergic rhinitis symptoms in primary schoolchildren six years apart in Budapest

Background: Few data are available concerning the time trends and risk factors associated with allergic rhinitis (AR) in schoolchildren in Hungary. Methods: At an interval of six years, parents of 6–12-year-old children completed identical ISAAC-based and additional questionnaires related to possible risk factors. Results: Response rate was 62.8% with 6335 questionnaires distributed in 2007, and 52.9% with 6441 questionnaires in 2013. The prevalence of current AR symptoms (subjects presenting clinical symptoms of AR in the past 12 months, but had yet to be diagnosed by physician) increased significantly from 14.9% to 23.5% (p < 0.001). There was no significant change in the prevalence of physician-diagnosed AR (11.6–11.2%). In multivariate analysis, gender (OR 0.733; CI 0.642–0.931), a family history of atopy (OR 2.017; CI 1.669–2.436), frequent upper respiratory tract infections (OR 2.033; CI 1.659–2.492), long-lasting disease before the appearance of the allergy (OR 2.119; CI 1.311–3.428), feather bedding (OR 0.773; CI 0.599–0.996) and living in a green area (OR 1.367; CI 1.133–1.650) were found to be significant risk factors of cumulative AR in 2013. In both of the groups with (p < 0.000) or without (p < 0.003) AR the families with a history of atopy used feather bedding less frequently than families without atopy. Conclusion: Although the prevalence of physician-diagnosed AR has not shown significant changes during the studied interval, the significant increase of the current AR symptoms suggests growing prevalence of AR among children in Budapest. Our results revealed new aspects of bedding customs in atopic families (AU)

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Survivin in autoimmune diseases.

Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4+ and CD8+ memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.

Trends in prevalence and risk factors of allergic rhinitis symptoms in primary schoolchildren six years apart in Budapest.

BACKGROUND: Few data are available concerning the time trends and risk factors associated with allergic rhinitis (AR) in schoolchildren in Hungary. METHODS: At an interval of six years, parents of 6-12-year-old children completed identical ISAAC-based and additional questionnaires related to possible risk factors. RESULTS: Response rate was 62.8% with 6335 questionnaires distributed in 2007, and 52.9% with 6441 questionnaires in 2013. The prevalence of current AR symptoms (subjects presenting clinical symptoms of AR in the past 12 months, but had yet to be diagnosed by physician) increased significantly from 14.9% to 23.5% (p<0.001). There was no significant change in the prevalence of physician-diagnosed AR (11.6-11.2%). In multivariate analysis, gender (OR 0.733; CI 0.642-0.931), a family history of atopy (OR 2.017; CI 1.669-2.436), frequent upper respiratory tract infections (OR 2.033; CI 1.659-2.492), long-lasting disease before the appearance of the allergy (OR 2.119; CI 1.311-3.428), feather bedding (OR 0.773; CI 0.599-0.996) and living in a green area (OR 1.367; CI 1.133-1.650) were found to be significant risk factors of cumulative AR in 2013. In both of the groups with (p<0.000) or without (p<0.003) AR the families with a history of atopy used feather bedding less frequently than families without atopy. CONCLUSION: Although the prevalence of physician-diagnosed AR has not shown significant changes during the studied interval, the significant increase of the current AR symptoms suggests growing prevalence of AR among children in Budapest. Our results revealed new aspects of bedding customs in atopic families.

Biodegradable airway stents in infants - Potential life-threatening pitfalls.

OBJECTIVE: The solution of severe tracheobronchial obstructions in early childhood means a great challenge. Biodegradable stents were intended to be a minimally invasive temporary solution which may decrease the number of interventions and limit the possible complications of stenting procedures. However, our first experiences have brought out a new, - especially in childhood - potentially life-threatening complication of this concept. METHODS: Five SX-ELLA biodegradable polydioxanone stents was applied in three patients because of severe tracheobronchial obstruction: congenital tracheomalacia (7 day-old), acquired tracheomalacia (10 month-old), and congenital trachea-bronchomalacia (10 month-old). RESULTS: The breathing of all children improved right after the procedure. We observed degradation of the stent from the 5th postoperative week which resulted in large intraluminar fragments causing significant airway obstruction: one patient died of severe pneumonia, the other baby required urgent bronchoscopy to remove the obstructing 'foreign body' from the trachea. In the third case repeated stent placements successfully maintained the tracheal lumen. CONCLUSIONS: Polydioxanone stents may offer an alternative to metallic or silastic stents for collapse or external compression of the trachea in children; however, large decaying fragments mean a potential risk especially in the small size pediatric airway. The fragmentation of the stent, which generally starts in the 4-6 postoperative weeks, may create large sharp pieces. These may be anchored to the mucosa and covered by crust leading to obstruction. As repeated interventions are required, we do not consider the application of biodegradable stents unambiguously advantageous.

Graphene oxide vs. reduced graphene oxide as carbon support in porphyrin peroxidase biomimetic nanomaterials.

The paper describes the preparation of supramolecular assemblies of tetrapyridylporphyrin (TPyP) and its metallic complexes with graphene oxide (GO) and thermally reduced graphene oxide (TRGO). The two carbon supports are introducing different characteristics in the absorption spectra of the investigated nanocomposites. Raman spectroscopy shows that the absorption of iron-tetrapyridylporphyrin is more efficient on GO than TRGO, suggesting that oxygen functionalities are involved in the non-covalent interaction between the iron-porphyrin and graphene. The biomimetic peroxidase activity is investigated and the two iron-containing composites exhibit a better catalytic activity than each component of the assembly, and their cobalt and manganese homologues, respectively. The main advantages of this work include the demonstration of graphene oxide as a very good support for graphene-based nanomaterials with peroxidase-like activity (K(M)=0.292 mM), the catalytic activity being observed even with very small amounts of porphyrins (the TPyP:graphene ratio=1:50). Its potential application in the detection of lipophilic antioxidants (vitamin E can be measured in the 10(-5)-10(-4) M range) is also shown.

Physical factors limiting the spectral extent and band gap dependence of supercontinuum generation.

Based on simulations of femtosecond pulse propagation in water we elucidate the physical factors that limit the attainable spectral extent of supercontinuum generation in bulk media. In contrast to the standard scenario, where arrest of self-focusing collapse by multiphoton absorption and plasma defocusing are viewed as imposing a limit to supercontinuum broadening, we show that linear chromatic dispersion also plays a major role. This insight provides an intuitive explanation of the observed band gap dependence of the attainable supercontinuum generation in condensed media.

Comparative in vitro studies on native and recombinant human cationic trypsins. Cathepsin B is a possible pathological activator of trypsinogen in pancreatitis.

Hereditary pancreatitis, an autosomal dominant disease is believed to be caused by mutation in the human trypsinogen gene. The role of mutations has been investigated by in vitro studies using recombinant rat and human trypsinogen (TG). In this study we compare the enzymatic properties and inhibition by human pancreatic secretory trypsin inhibitor (hPSTI) of the native, postsynthetically modified and recombinant cationic trypsin, and found these values practically identical. We also determined the autolytic stability of recombinant wild type (Hu1Asn21) and pancreatitis-associated (Hu1Ile21) trypsin. Both forms were equally stable. Similarly, we found no difference in the rate of activation of the two zymogens by human cationic and anionic trypsin. Mesotrypsin did not activate either form. The rate of autocatalytic activation of Hu1Asn21 TG and Hu1Ile21 TG was also identical at pH 8 both in the presence and absence of Ca2+. At pH 5 Hu1Ile21 TG autoactivated about twice as fast as Hu1Asn21 TG. The presence of physiological amount of hPSTI completely prevented autoactivation of both zymogens at pH 8 and at pH 5 as well. Cathepsin B readily activated both zymogens although Hu1Ile21 TG was activated about 2.5-3 times as fast as Hu1Asn21 TG. The presence of hPSTI did not prevent the activation of zymogens by cathepsin B. Our results underlie the central role of cathepsin B in the development of different forms of pancreatitis.

[Objective audiologic assessment of children treated with amikacin]. / Amikacinnal kezelt gyermekek objektív audiológiai vizsgálata.

Hearing assessment of 14 children suffered from urinary tract infection and treated by amikacin is reported. The dosage of amikacin was 7.5 mg/kg/daily for 10 days and the serum level of amikacin not exceeded the 35 mcg/ml. The aim of the study was on the one hand to determine the hearing damaging side effect of amikacin and on the other to assess the usefulness of objective methods for detection of hearing loss in this population. Authors used for screening a transient otoacoustic emission (TEOAE) during and after (2-4 weeks) therapy. If subjective and objective (TEOAE) methods gave a good result, no further checkup has considered as necessary, but if there were no evoked emission, acoustic brainstem response audiometry has been carried out for verification. It result no hearing loss could be detected in the measured specimen. In conclusion it has been stated that by proper dosage and serum level screening amikacin may no lead to hearing loss in children, and objective methods are valuable for hearing screening and monitoring of such population of children.

[Aortopexy as a surgical treatment method in infantile congenital tracheo-chondrohypoplasia and tracheomalacia]. / Aortopexia, mint a csecsemökori congenitalis tracheo-chondrohypoplasia és a tracheomalatia mütéti kezelése.

Congenital tracheal chondrohypoplasia and tracheomalacia have come to present a significant challenge in recent paediatric surgery. Authors shortly describe their pathology, pathophysiology, symptoms, diagnostic evaluation and outline the most frequency surgical procedures for them. The first three aortopexies in the authors' departments are described in this paper, with particular attention paid to the clinical problems of congenital tracheal chondrohypoplasia and tracheomalacia and the role of this method in surgical treatment, respectively. Aortopexy is quick, easy to carry out and atraumatic for the growing trachea. Authors want to draw attention to the fact that not every form of congenital tracheal chondrohypoplasia and tracheomalacia may be treated by conservative therapy, and that surgical treatment is recommended not only for life threatening forms, but for other severe forms as well.

Nosocomial Streptococcus pneumoniae infection causing children's acute otitis media.

Streptococcus pneumoniae is the most frequent pathogen in young children's acute otitis media. It also plays a significant role in nosocomial ear infection in children, while it causes pneumonia with or without bacteremia in hospitalized elderly people. Multiple antibiotic resistant strains are prevalent among S. pneumoniae isolates from the respiratory tract of hospitalized patients in Hungary. This fact makes therapeutic reconsiderations concerning the use of oral beta-lactams mandatory. In this retrospective study two nosocomial outbreaks caused by multiresistant S. pneumoniae in two pediatric hospitals are described. The patients admitted with a chronic underlying disease (milk intolerance and gastro-oesophageal reflux were predominant) or respiratory tract infection acquired acute otitis media. Therapy with oral beta-lactams (first and second generation cephalosporins and amoxicillin), macrolides and co-trimoxazole was ineffective in most of the cases or resulted in transient improvement. In some cases acute otitis media resolved with the improvement of the underlying condition, in two cases administration of cefotaxime resulted in recovery and in one case mastoidectomy became necessary.

[Evaluation of hearing loss by means of inner ear acoustic emission in neonates treated with aminoglycoside]. / Halláskárosodás megítélése a belsö fül hangenergia kibocsátásának segítségével aminoglikoziddal kezelt újszülöttekben.

Despite their ototoxic and other side effects, aminoglycosides are still widely used in the treatment of neonatal infections. A novel method for evaluation of hearing loss is distortion product otoacoustic emission (DPOAE). Physiologic acoustic energy-emission produced by sound stimulus in the inner ear is detected by DPOAE. Existing acoustic emission indicates the functional integrity of the inner ear. DPOAE was performed in 19 newborns treated with netilmicin for different infections. Serum netilmicin levels did not exceed 12 mg/l; renal functions were normal. Existence of emission was detected in 15 newborns. There was no emission found in 4 newborns unilaterally, which was fully restored in 2 months. In conclusion, aminoglycosides have no considerable ototoxic side effects. DPOAE is thought to be an objective, fast, and non-invasive method for hearing screening in the newborn period.

[Simultaneous occurrence of moyamoya disease and subclavian steal syndrome]. / A moyamoya betegség és a subclavian steal syndroma együttes elöfordulása.

The authors present a case of moyamoya disease associated with subclavian steal syndrome. They could not find any report in literature about the combination of these syndromes. The Doppler, MR, and angiographic findings as well as the clinical importance of subclavian steal and moyamoya syndromes are briefly summarized.

Transitory evoked otoacoustic emission (TEOAE) in a child with profound hearing loss.

The case of a 3-month-old, prematurely born boy with auditory brainstem response (ABR), verified profound hearing loss and normal transitory evoked otoacoustic emission is presented. Isolated retrocochlear deafness which did not influence TEOAE is hypothesised as a possible cause. The critical evaluation of results when using TEOAE as a screening method is suggested.

[Hearing loss resulting from purulent meningitis in the light of adjuvant dexamethasone therapy]. / A purulens meningitist követö halláskárosodás az adjuváns dexamethason kezelés tükrében.

Results of objective audiometry of 109 infants and children after purulent meningitis are presented. Among them 17 patients got dexamethasone as a supportive therapy. There was no statistically significant difference in hearing loss between the dexamethasone-treated and the control group. (41 vs 43% sensorineural hearing loss respectively). Authors do not contraindicate the dexamethasone therapy in purulent meningitis because of its harmlessness and useful effect to the course of the disease but further investigations are needed for avoidance of hearing loss following meningitis.

[Otoacoustic emission audiometry in neonates and adults]. / Otoakusztikus emissziós hallásvizsgálat újszülött- és felnöttkorban.

The authors discuss the clinical use of the otoacoustic emission audiometry. During the physiological process of sound amplification in the cochlea vibration energy escapes from the inner ear. By the analysis of this sound it is possible to gain information about the function of the cochlea. According to the experiences of the authors the method is extremely useful for screening audiometry in pathological and normal neonates. In adults it can be used for monitoring the cochlear function during ototoxic therapy or noise exposure.

Epipharyngeal teratoma in infancy.

Epipharyngeal teratomas are rare congenital lesions that often cause respiratory distress, stridor at birth. The management of such anomalies should include establishment of secure upper airways, radiographic exclusion of midline CNS malformations and early surgical excision to prevent malignant transformation, asphyxia or permanent facial distortion. The diagnosis of congenital stridor, dyspnea and rhinitis should be performed very carefully.