Five-Year Experience In Surgical Treatment Of Temporal Bone Paragangliomas

The article describes our five-year experience in the surgical treatment of temporal bone paragangliomas. Considering our experience, the surgical treatment of patients with different types of paragangliomas based on a detailed study of the CT scan and MRI data using the preoperative selective embolization of tumor-feeding vessels and the navigation system intraoperatively as well as the endoscopy assistance allows total removing of the tumor with minimal damaging of the vital structures of the lateral skull base

Вплив похідних тіазолідину на варіабельність серцевого ритму і показники крові експериментальних тварин за умов гіпобаричної гіпоксії

Heart rate variability (HRV ) parameters and hematological indices in rats under hypobaric hypoxia duringtreatment by a thiazolidine derivative substance Les-589 (potassium salt of 3-(5-phenylpropeniliden rhodamine-3-yl)-propanoic acid) were studied. Hypobaric hypoxia was developed in altitude chamber for 1 hour under conditionsidentical height of 6000 m above sea level, 45 minutes after injection of Les-589. Thiotriazolin was applied as areference drug.After one day after exposure to hypoxia, according to blood parameters and hematological indices, adaptiveresponse develops by the type of insufficient adaptation. The effect of the prior administration of Les-589, similar tothe effect of a reference drug Thiotriazolin, in the time of post-hypoxic period developed reactions of an increasedactivation, which indicates a favorable course of adaptation.Considering the parameters of HRV was found that prior administration of Les-589 within studied terms of posthypoxicperiod leads to earlier and more effective recovery of various links of regulatory systems, compared withhypoxia. This is consistent with an estimated type of adaptation processes, based on hematological parametersand indices.Исследовали параметры вариабельности сердечного ритма, а также гематологические показатели и индексы у крыс при гипобарической гипоксии на фоне применения производной тиазолидина – вещества Les-589 (калийная соль 3-(5-фенилпропенилиденроданин-3-ил)-пропионовой кислоты). Гипобарическую гипоксию моделировали в барокамере в течение 1 ч в условиях, идентичных высоте 6000 м над уровнем  моря, через 45 мин после введения Les-589. Как эталонный препарат использовали тиотриазолин.Через сутки после влияния гипоксии, судя по показателям крови и гематологическим индексам, приспособительная реакция развивается по типу неполноценной адаптации. В отличие от этого, эффект предварительного введения Les-589, аналогично эффекту тиотриазолина как эталонного препарата, в этот срок постгипоксического периода реализуется реакцией повышенной активации, что свидетельствует о благоприятном развитии адаптации.На основании параметров вариабельности сердечного ритма установлено, что предварительное  введение Les-589 в исследуемые сроки постгипоксического периода приводит к более быстрому и эффективному восстановлению уровня различных звеньев регуляторных систем по сравнению с гипоксией. Это соответствует определенному на основании гематологических показателей и индексов типу развития адаптационных процессовДосліджували параметри варіабельності серцевого ритму, а також гематологічні показники та індекси в щурів при гіпобаричній гіпоксії на фоні застосування похідної тіазолідину – речовини Les-589 (калійна сіль3-(5-фенілпропеніліденродамін-3-іл)-пропанової кислоти). Гіпобаричну гіпоксію моделювали у барокамері впродовж 1 год за умов, ідентичних висоті 6000 м над рівнем моря, через 45 хв після введення Les-589. Якеталонний препарат використовували тіотріазолін. Через добу після впливу гіпоксії, з огляду на показники крові та гематологічні індекси, пристосуваль-на реакція розвивається за типом неповноцінної адаптації. Натомість ефект попереднього введення Les-589, аналогічно до ефекту тіотріазоліну як еталонного препарату, в цей термін постгіпоксичного періоду реалізується реакцією підвищеної активації, що свідчить про сприятливий перебіг адаптації. На основі параметрів варіабельності серцевого ритму встановлено, що попереднє введення Les-589 у досліджувані терміни постгіпоксичного періоду призводить до швидшого й ефективнішого відновлення рівня різних ланок регуляторних систем порівняно з гіпоксією. Це узгоджується з визначеним на основі гематологічних показників та індексів типом розвитку адаптаційних процесів

Iodine deficiency in pregnant women and newborns in the Saratov region: current state of the problem

Introduction. Iodine deficiency remains an urgent challenge for the Russian Federation. Pregnant women should receive prophylactic potassium iodide supplements at a dose of 200–250 mcg per day. To monitor the severity of iodine deficiency in the regions and the efficacy of prenatal iodine prophylaxis, it is prudent to use the neonatal hyperthyrotropinemia rate for newborns (thyroidstimulating hormone level is higher than 5 μIU/L) based on the results of congenital hypothyroidism screening.Objective. To assess the changes in the severity of iodine deficiency and the efficacy of iodine prophylaxis in pregnant women and newborns in the Saratov region based on the incidence of neonatal hyperthyrotropinemia over the past 25 years.Materials and methods. The incidence of neonatal hyperthyrotropinemia in newborns in the Saratov region for the period of 1996–2000 and 2015–2020 was analysed. In total, 229,625 children were examined.Results and discussion. In 1996–2000, neonatal hyperthyrotropinemia was detected in 37.4% of newborns, which was evidence of the presence of moderate iodine deficiency in the region. In 2015–2020, the incidence of neonatal hyperthyrotropinemia decreased by 5.42 times to 6.9% (p < 0.0001) against the background of group iodine prophylaxis in pregnant women, but remained higher than the World Health Organization targets for iodine-rich regions (<3%) suggesting the preservation of mild iodine deficiency in pregnant women and newborns in the Saratov region.Conclusions. Despite the obligatory doctor’s prescription of prenatal group iodine prophylaxis, there is still iodine insufficiency in pregnant women and newborns in the Saratov region, which requires further improvement of the regional iodine deficiency eradication action system in the risk groups. However, significant advances in the fight against iodine deficiency in the nutrition of the Russian population can only be achieved after the adoption of the federal law on universal salt iodization

Сравнение колориметрического и электрохимического (анализатор Easy Touch GCU) методов определения уровня мочевой кислоты в крови у пациентов с подагрой и гиперурикемией в клинической практике (данные пилотного исследования)

   Hyperuricemia (HU) is a condition caused by an increase in serum uric acid (UA) levels above 360 μmol/l. Often HU is asymptomatic, but under the influence of genetic and environmental factors, attacks of peripheral arthritis (gout) may occur. Remission of gout is achieved by normalization of UA serum levels, which can be determined by a colorimetric or electrochemical method, although the latter is not currently commonly used in clinical practice to control UA levels.   Objective: to compare the standard colorimetric and electrochemical methods (Easy Touch GCU Meter) for monitoring UA levels.   Material and methods. 30 gout patients were included in the study. This group included subjects with current/anamnestic asymptomatic HU andpatients with a confirmed diagnosis of gout (ACR/EULAR 2015 criteria). The examination included a general examination, history taking, and laboratory testing. The determination of UA level by the colorimetric method in venous blood serum was performed no later than 5 minutes after collection, and the determination of UA level in fresh whole capillary blood from the fingertip by the electrochemical method (Easy Touch GCU Meter) – immediately after collection.   Results and discussion. The average values of UA blood level determined by the two compared methods differed by 13.9 μmol/l (3.9 % with respect to the colorimetric method). The high value of the correlation coefficient (r = 0.86) indicates a close linear relationship between the compared results and their good agreement. The method is also applicable in patients with achieved normouricemia.   Conclusions. The method of electrochemical determination of UA level in subjects with HU and gout can be used in real clinical practice for self-monitoring.   Гиперурикемия (ГУ) – состояние, вызванное повышением уровня мочевой кислоты (МК) сыворотки крови >360 мкмоль/л. Зачастую ГУ бывает асимптоматической, однако под влиянием ряда генетических факторов, а также факторов внешней среды она может проявляться в виде приступов периферического артрита (подагры). Условием для ремиссии данного заболевания является достижение нормальных значений МК, которые могут быть определены стандартным колориметрическим методом или электрохимическим методом, последний в настоящее время не распространен в клинической практике для контроля урикемии.   Цель исследования – сравнение результатов определения уровня МК с помощью стандартного колориметрического и электрохимического (анализатор Easy Touch GCU) методов контроля уровня урикемии в клинической практике.   Материал и методы. В исследование включено 30 больных подагрой. В эту группу вошли лица с асимптоматической ГУ в настоящее время/в анамнезе и пациенты с достоверным диагнозом подагры, соответствующим критериям ACR/EULAR 2015 г. Проводили общий осмотр, сбор анамнеза, лабораторное исследование. Определение уровня МК колориметрическим методом в сыворотке венозной крови выполнялось не позднее чем через 5 мин после ее получения, а определение уровня МК в свежей цельной капиллярной крови из кончика пальца электрохимическим методом (анализатор Easy Touch GCU) – немедленно после ее получения.   Результаты и обсуждение. Средний уровень МК в крови, исследованный двумя сравниваемыми методами, различался на 13,9 мкмоль/л (3,9 % по отношению к колориметрическому методу). Высокое значение коэффициента корреляции (r = 0,86) свидетельствует о тесной линейной связи сравниваемых результатов при их хорошей согласованности. Метод применим и к пациентам с достигнутой нормоурикемией.   Заключение. Метод электрохимического определения уровня МК у лиц с ГУ и подагрой может быть использован для самоконтроля в реальной клинической практике

Electromagnetic-field quantization and spontaneous decay in left-handed media

We present a quantization scheme for the electromagnetic field interacting with atomic systems in the presence of dispersing and absorbing magnetodielectric media, including left-handed material having negative real part of the refractive index. The theory is applied to the spontaneous decay of a two-level atom at the center of a spherical free-space cavity surrounded by magnetodielectric matter of overlapping band-gap zones. Results for both big and small cavities are presented, and the problem of local-field corrections within the real-cavity model is addressed.Comment: 15 pages, 5 figures, RevTe

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

Simultaneous Detection of Circulating Autoreactive CD8+ T-Cells Specific for Different Islet Cell–Associated Epitopes Using Combinatorial MHC Multimers

textabstractOBJECTIVE - Type 1 diabetes results from selective T-cell-mediated destruction of the insulin-producing β-cells in the pancreas. In this process, islet epitope-specific CD8+T-cells play a pivotal role. Thus, monitoring of multiple islet-specific CD8+T-cells may prove to be valuable for measuring disease activity, progression, and intervention. Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive. RESEARCH DESIGN AND METHODS - Here, we used a combinatorial quantum dot major histocompatibility complex multimer technique to simultaneously monitor the presence of HLA-A2 restricted insulin B10-18, prepro-insulin (PPI)15-24, islet antigen (IA)-2797-805, GAD65114-123, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)265-273, and pre-pro islet amyloid polypeptide (ppIAPP)5-13-specific CD8+T-cells in recent-onset diabetic patients, their siblings, healthy control subjects, and islet cell transplantation recipients. RESULTS - Using this kit, islet autoreactive CD8+T-cells recognizing insulin B10-18, IA-2797-805, and IGRP265-273were shown to be frequently detectable in recent-onset diabetic patients but rarely in healthy control subjects; PPI15-24proved to be the most sensitive epitope. Applying the "Diab-Q-kit" to samples of islet cell transplantation recipients allowed detection of changes of autoreactive T-cell frequencies against multiple islet cell-derived epitopes that were associated with disease activity and correlated with clinical outcome. CONCLUSIONS - A kit was developed that allows simultaneous detection of CD8+T-cells reactive to multiple HLA-A2-restricted β-cell epitopes requiring limited amounts of blood, without a need for in vitro culture, that is applicable on stored blood samples

Comparative genomics and evolution of bacterial regulatory systems

Abstract: Recent advances in genome sequencing and development of comparative genomics techniques allow one to study evolution of regulation in prokaryotes at several different levels: microevolution of orthologous regulatory sites, changes in regulon content, evolution of interacting regulatory systems, and co-evolution of transcription factors and their binding signals. Regulatory interactions appear to be very dynamic in some cases and surprisingly stable in others. The review presents several examples where comparative analysis uncovered plausible scenarios of evolution of regulatory systems

Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis

BACKGROUND: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s) involved in the type shift. METHODOLOGY/PRINCIPAL FINDING: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. CONCLUSION/SIGNIFICANCE: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis