Non-Immunoglobulin-E mediated gastrointestinal food allergy in children: diagnosis, management and clinical impact

Background: Despite all research published in the last decades, the prevalence of food allergy in the paediatric population has continued to increase and is nowadays recognized as a significant public health problem. In the United Kingdom, studies have found that between 2.2% and 5.5% of the infants in the first year of life present with proven food allergies, with the prevalence of cow’s milk protein allergy, the most common form of non-IgE food allergies, ranging between 1.9% and 4.9%. The diagnosis of non-IgE mediated food allergy is a real challenge due to its delayed onset, with symptoms occurring hours to days after ingestion of the culprit and mainly affecting the gastrointestinal tract. Allergy tests have shown limited use in these patients, and the diagnosis relies heavily on the recognition of symptoms and an allergy-focused history. The treatment is based on diet elimination, which can lead to the development of nutritional disorders and negative impact on the child’s quality of life. Objectives: The aims of the publications included in this thesis are, first, to prospectively investigate the required length of elimination diet to achieve symptom improvement during the diagnostic process; second, to evaluate the knowledge of primary health care professionals about diagnosis and management of cow’s milk protein allergy, to compare with parents views and opinions, and to better understand diagnosis tools, treatment and tolerance in infants diagnosed with nonIgE food allergies; third, to evaluate possible impacts of the elimination diet on growth and nutrients deficiencies; and fourth, to analyse the potential impact of nonIgE mediated gastrointestinal allergies on the quality of life of the affected children and their families. Methods: Children with suspected non-IgE mediated gastrointestinal food allergies were recruited and followed prospectively at a large tertiary gastroenterology department in the United Kingdom (UK) from December 2011 to November 2013. This study was designed to investigate the impact of non-IgE mediated food allergies on quality of life, as well as to establish symptoms, children’s growth and the characteristics and impact of dietary elimination. The knowledge and journey of diagnosis of cow’s milk protein allergy among general practitioners were studied via surveys. Eosinophilic colitis in infants was studied through a systematic review. II Results: In non-IgE mediated gastrointestinal food allergies the required time to achieve symptom improvement following the initiation of the elimination diet was four weeks in 98% of our patients. All symptoms individually and collectively have statistically improved after commencing the elimination diet (p <0.001). Regarding cow’s milk protein allergy, parents and general practitioners have very different perceptions about the course of the disease and the families’ journeys. An extensive review of the literature found that eosinophilic colitis occurred more frequently in male infants, younger than six months old. Half were exclusively breastfed at the time of the diagnosis. Patients on a diagnostic four-week elimination diet showed an improvement in the weight-for-age and weight-for-height. It was also noted that 60% of the cohort had low vitamin D intake and a higher number of patients had a low intake of copper, zinc, and selenium. Non-IgE mediated food allergies have a negative impact on the quality of life of the affected children and their families. Conclusions: The “Discovering the effect of non-IgE mediated allergies on children and their families” is a landmark study in the paediatric food allergy field. This welldesigned study investigated and elucidated some important characteristics and clinical features of this group of patients. Its impact is reflected in the number of publications derived from the results of this cohort, a large number of citations and the impact in clinical practice worldwide as much more is now known about this condition. Studies investigating preventative measures for the development of food allergies in childhood are also essential in the future

Sorption of microorganisms by wide-porous agarose cryogels containing grafted aliphatic chains of different length

The possibility of fractionation of heterogeneous bacterial populations using wide-porous agarose cryogels containing grafted aliphatic groups with the chain lengths of 4, 7, and 12 carbon atoms was demonstrated for the first time. The maximum sorption of vegetative cells of gram-positive bacteria (60%) was shown for the polymeric carrier with the chain length of 4 carbon atoms, while the hypometabolic cells appearing in the population after prolonged (60-day) cultivation were trapped by wide-porous affinity sorbents with C7- and C12- aliphatic groups much better than vegetative cells. © Pleiades Publishing, Ltd 2009

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study)

Introduction: Peanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy. Methods and analysis: 200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention arms—PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group. Ethics and dissemination: This study has been approved by the Human Research Ethics Committees at the Royal Children’s Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Adriana Chebar Lozinsky, Paxton Loke, Francesca Orsini, Michael O’Sullivan, Susan L. Prescott, Michael S Gold, Patrick Quinn, Audrey DunnGalvin, Mimi LK Tang, on behalf of the PPOIT study tea

Криогели поливинилового спирта, сформированные из растворов полимера в диметилсульфоксиде с добавками тетраметоксисилана

Organic–inorganic hybrid cryogels of poly(vinyl alcohol) (PVA) containing silica inclusions (SiO2) were obtained and studied. Such inclusions were formed in the course of hydrolytic polycondensation (sol-gel process) of tetramethoxysilane (TMOS) introduced into concentrated polymer solutions in dimethyl sulfoxide (DMSO). PVA concentration in these solutions was 60, 80 or 100 g/L; while the concentration of TMOS was varied in a range of 0.15–0.61 mol/L. The polymer solutions were subjected to the cryogenic treatment at temperatures by 40 °С lower than DMSO crystallization temperature (+18.4°C). The frozen samples were thawed out at a heating rate of 0.03°/min. It is shown that moderate freezing at −21.6 °C, then frozen storage and subsequent thawing of the initial reaction mixture PVA/DMSO/TMOS/acid catalyst resulted in the formation of strong macroporous PVA/SiO2 cryogels. Such cryogel materials are hybrid systems, because the gel-forming polymer and the silica containing moieties belong to the content of the gel phase. The basis of this intermolecular interaction is hydrogen bonding between OH groups of the adjacent chains. This leads to the formation of modified microcrystallinity zones that perform as the nodes of the three-dimensional network of cryogels. The effects of significant increase in their rigidity and heat-resistance with increasing PVA and TMOS concentration in the initial feed were also observed. It was shown that the success of the synthesis of transparent elastic and heat-resistant PVA/SiO2 cryogels depends on the choice of the optimal ratio between the precursors and the combined effect of the liquid (methanol and water) and silicon-containing components on the formation of multiple hydrogen bonds and microcrystallites.Получены и исследованы органо-неорганические гибридные криогели поливинилового спирта (ПВС), содержащие кремнеземную составляющую (SiO2), образующуюся в результате реакций гидролитической поликонденсации (золь-гель-процесса) тетраметоксисилана (ТМОС), вводимого в исходный концентрированный раствор полимера в диметилсульфоксиде (ДМСО). Содержание ПВС в таких растворах составляло 60, 80 или 100 г/л; концентрацию ТМОС варьировали от 0.15 до 0.61 моль/л; криогенную обработку растворов полимера проводили при температуре, на 40° ниже точки кристаллизации чистого ДМСО (+18.4 °C); замороженные образцы оттаивали, нагревая со скоростью 0.03°/мин. Показано, что неглубокое замораживание (–21.6 °C), выдерживание в замороженном состоянии и последующее оттаивание исходной реакционной смеси ПВС/ДМСО/ТМОС/кислотный катализатор приводит к формированию прочных макропористых криогелей ПВС/SiO2. Полученные криогелевые материалы являются гибридными в связи с возникновением устойчивых контактов макромолекулы ПВС–олигосилоксаны, движущей силой такого межмолекулярного взаимодействия является водородное связывание между ОН-группами соседних цепей, приводящее к образованию модифицированных зон микрокристалличности, выполняющих функцию узлов пространственной сетки криогелей. Установлены эффекты существенного возрастания жесткости и теплостойкости криогелей ПВС/SiO2 по мере повышения концентрации ПВС и ТМОС в исходной системе. Показано, что успех синтеза прозрачных упругих и термостойких криогелей ПВС/SiO2 зависит как от нахождения оптимального соотношения между исходными веществами, так и от совместного воздействия жидких (метанол и вода) и кремнийсодержащих компонентов на процессы образования множественных водородных связей и микрокристаллитов.

Two-Photon Fluorescence Microscopy Imaging of Cellular Oxidative Stress Using Profluorescent Nitroxides

A range of varying chromophore nitroxide free radicals and their nonradical methoxyamine analogues were synthesized and their linear photophysical properties examined. The presence of the proximate free radical masks the chromophore’s usual fluorescence emission, and these species are described as profluorescent. Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7 and 19, respectively) exhibited two-photon absorption (2PA) cross sections of approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese hamster ovary (CHO) cells. Imaging colocalization experiments with the commercially available CellROX Deep Red oxidative stress monitor demonstrated good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes to H2O2-induced damage was also demonstrated by both one- and two-photon fluorescence microscopy. These profluorescent nitroxide probes are potentially powerful tools for imaging oxidative stress in biological systems, and they essentially “light up” in the presence of certain species generated from oxidative stress. The high ratio of the fluorescence quantum yield between the profluorescent nitroxide species and their nonradical adducts provides the sensitivity required for measuring a range of cellular redox environments. Furthermore, their reasonable 2PA cross sections provide for the option of using two-photon fluorescence microscopy, which circumvents commonly encountered disadvantages associated with one-photon imaging such as photobleaching and poor tissue penetration

Индукция остеогенеза костной ткани нижней челюсти кролика с использованием криогенно‑структурированного губчатого альбуминового 3D-носителя, нагруженного биорегулятором

Objective: to study the induction of osteogenesis caused by introducing into the defect area broadly porous cryogenically structured 3D carriers, based on serum albumin and loaded with a bioregulator isolated from bovine serum on an experimental model of mandible defect in rabbits in vivo.Materials and methods. Cryogenically structured sponges in the form of cylindrical specimens, 5 mm in diameter and 5 mm in height, prepared from bovine serum albumin, were used as the bioregulator carrier. The experimental laboratory animals were male Chinchilla rabbits, weighing 2–2.5 kg. Bone tissue was skeletonized under anesthesia (intramuscular anesthetic Zoletil 100) with a 3-cm incision in the angle of the mandible and a 5-mm-diameter cutter was used to create a 2–3-mm deep defect to install an appropriate-size albumin sponge. A total of 24 animals participated in the experiment. X-ray control of the defect area was performed in vivo on day 14 using PanExam+ (Kavo) device (20 m X-ray). Histological examination of tissues was carried out at day 30 after the defect using a light microscope.Results. Experiments performed indicate an active restoration of bone tissue in the extensive defect area when using an albumin-based 3D carrier with the inclusion of a bioregulator as compared to the control experiments. There were osteointegrative and osteoinductive processes, almost complete decomposition (biodegradation) of albumin sponge with formation of islands of dense bone tissue with small foci of coarse fibrous tissue in the defect. This demonstrated good dynamics of recovery processes at this stage of healing.Conclusion. Under the action of a serum bioregulator contained in an albumin-based sponge, the repair process leads to restoration of normal bone tissue without formation of bone callus and altered bone tissue different from the native one.Цель работы: изучить in vivo на модели экспериментального костного дефекта нижней челюсти кролика индукцию остеогенеза, вызываемую внесением в область дефекта широкопористых криогенно-структурированных 3D-носителей на основе сывороточного альбумина, нагруженных биорегулятором, выделенным из сыворотки крови крупного рогатого скота.Материалы и методы. В качестве носителя биорегулятора использовали криогенно-структурированные губки в виде цилиндрических образцов диаметром 5 мм и высотой также 5 мм, приготовленные из бычьего сывороточного альбумина. Эксперименты с лабораторными животными проводили на кроликах породы Шиншилла весом 2–2,5 кг, самцах. Под наркозом (внутримышечный наркоз Zoletil 100) разрезом до 3 см в области угла нижней челюсти скелетировали костную ткань и фрезой диаметром 5 мм создавали дефект глубиной 2–3 мм для установки альбуминовой губки соответствующего размера. Всего в эксперименте присутствовало 24 животных. Проводили рентгенологический контроль области дефекта на 14-е сутки прижизненно на аппарате PanExam+ (Kavo), 20 мРентген. Гистологическое исследование тканей проводили на 30-е сутки после нанесения дефекта с использованием светового микроскопа.Результаты. Результаты проведенных экспериментов свидетельствуют об активном восстановлении костной ткани в области обширного дефекта при использовании альбуминового 3D-носителя именно с включением биорегулятора по сравнению с контрольными опытами. Зарегистрированы процессы остеоинтегративной и остеоиндуктивной активности, практически полное разложение (биодеградация) альбуминовой губки с формированием на месте дефекта островков плотной костной ткани с небольшими очагами грубоволокнистой ткани, что говорит о хорошей динамике восстановительных процессов на данном сроке заживления.Заключение. Полученные данные указывают на то, что под действием сывороточного биорегулятора в составе альбуминовой губки процесс репарации приводит к восстановлению нормальной костной ткани без формирования костной мозоли и измененной костной ткани, отличной от нативной ткани