РИСК РАЗВИТИЯ ПНЕВМОНИИ И ПОЛИМОРФИЗМ ГЕНОВ TLR2 И TLR4: МЕТА-АНАЛИЗ

Pneumonia is one of the most common infections with high mortality rates. The gene polymorphism of Toll-like receptors that belong to the first line of defense of the immune system can make a considerable contribution to individual variability due to the risk of pneumonia. Today this issue has not been adequately explored and the data available in the literature are conflicting.Objective: to carry out a meta-analysis of the association between Toll-like receptor gene polymorphic variants and the risk of pneumonias and its coinfections.Methods. A meta-analysis was carried out to detect a possible association of the risk of pneumonia and coinfections with single nucleotide polymorphisms (SNP) in the TLR2 (rs5743708 (2258 G>A; Arg753Gln) and TLR4 (rs4986790 (896A>G; Asp299Gly) genes. The investigation enrolled 2312 (682 patients/1630 control individuals) and 3075 (910/2165) Caucasians for each SNP, respectively. As the rate of minor alleles of both polymorphic variants was less than 5%; the analysis was made only for a dominant genetic model.Results. Analysis of the study group showed that the A allele of TLR2 rs5743708 was associated with the risk of pneumonia (OR = 1.90; 95% CI: 1.02—3.54; P=0.042) while TLR4 rs4986790 was not associated with pneumonia. Analysis of subgroups (children/adults and community-acquired/nosocomial pneumonia) revealed no significant effects.Conclusion. The A allele of TLR2 rs5743708 may be a risk factor for susceptibility to pneumonia. These results have promises for their clinical application; however, due to the high heterogeneity and insufficient sizes of samples, these results need to be confirmed by further investigations.Пневмония является одной из наиболее распространенных инфекций с высоким уровнем смертности. Полиморфизм генов толл-подобных рецепторов, относящихся к первой линии защиты иммунной системы, может вносить существенный вклад в индивидуальную вариабельность в связи с риском развития пневмонии. На сегодняшний день этот вопрос недостаточно изучен, а имеющиеся литературные данные противоречивы. Цель исследования. Мета-анализ ассоциации полиморфных вариантов генов толл-подобных рецепторов и риска развития пневмонии и сопутствующих ей инфекций. Методы. Для обнаружения возможной ассоциации риска развития пневмонии и сопутствующих инфекций с однонуклеотидными полиморфизмами (SNP) в генах TLR2 rs5743708 (2258 G>A; Arg753Gln) и TLR4 rs4986790 (896A>G; Asp299Gly) был выполнен мета-анализ. В исследование было включено 2312 (682 пациента / 1630 индивидуумов контрольной группы) и 3075 (910/2165) представителей европеоидной расы для каждого SNP соответственно. Так как частота минорных аллелей обоих полиморфных вариантов составляет менее 5%, анализ выполнен только для доминантной генетической модели. Результаты. При анализе общей группы аллель А гена TLR2 (rs5743708) показал ассоциацию с риском развития пневмонии (OR=1,90, 95% ДИ: 1,02—3,54, p=0,042), в то время как для гена TLR4 (rs4986790) ассоциации с пневмонией выявлено не было. При анализе подгрупп (дети/взрослые и внебольничная пневмония/нозокомиальная пневмония) значимые эффекты отсутствовали. Выводы. Аллель А гена TLR2 (rs5743708) может быть фактором риска восприимчивости к пневмонии. Данные результаты имеют перспективы для их использования в клинической практике, однако, в связи с высокой гетерогенностью и недостаточными размерами выборок, требуется подтверждение этих результатов в дальнейших исследованиях

EARLY NEOPROTEROZOIC CRUST FORMATON IN THE DZABKHAN MICROCONTINENT, CENTRAL ASIAN OROGENIC BELT

The Dzabkhan microcontinent was defined by [Mossakovsky et al., 1994] as a cratonic terrane with an early Precambrian basement that combines highgrade metamorphic complexes of the Songino, Dzabkhan, Otgon, Baidarik, Ider and Jargalant Blocks. However, early Precambrian ages have so far only been recognized in the Baidarik and Ider blocks [Kozakov et al., 2007, 2011; Kröner et al., 2015].The Dzabkhan microcontinent was defined by [Mossakovsky et al., 1994] as a cratonic terrane with an early Precambrian basement that combines highgrade metamorphic complexes of the Songino, Dzabkhan, Otgon, Baidarik, Ider and Jargalant Blocks. However, early Precambrian ages have so far only been recognized in the Baidarik and Ider blocks [Kozakov et al., 2007, 2011; Kröner et al., 2015]

Evaluation of a method for the determination of antibacterial activity of chitosan

© 2016, Pleiades Publishing, Inc.A method for the determination of the antimicrobial activity of chitosan with the use of organic salts for the production of pH in the range of 5.5–8.2 was studied. The double-dilution method demonstrated the effectiveness of the determination of the antimicrobial activity of chitosan samples with different molecular weights and solubilities. It was found that the antibacterial activity increased at low pH values with increasing molecular weight, but chitosans with a molecular weight of 5–6 kDa showed higher activity at neutral and slightly alkaline pH levels. Determination of the antimicrobial activity of various chitosan samples at different pH values allowed a more reliable assessment of the potential biological activity of chitosan

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy)

Non-steroidal anti-inflammatory drugs (NSAIDs) are most popular medications for the treatment of pain in common musculoskeletal diseases such as osteoarthritis (OA) and non-specific low back pain (LBP). However, the factors affecting the effectiveness of these drugs have not been determined fully. Aim: to identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. Materials and methods. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Results and discussion. Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (

Очень ранний клинический ответ при лечении ингибитором янус-киназ тофацитинибом у больных активным ревматоидным артритом: динамика боли и элементов центральной сенситизации

Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of >18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p<0.001), in pain according to the patient's assessment of the analgesic effect of therapy to 43.6±29.6%; in the median PainDETECT score to 2.5 [0; 8.7] (p<0.001); and in CSI scores to an average of 26.4±13.9 (p <0.001). No serious adverse reactions were noted.TOFA has a rapid analgesic effect, which allows it to be considered as a chooser for pathogenetic therapy in patients with active RA and severe pain, especially in the presence of CS signs and secondary fibromyalgia. Undoubtedly, large-scale, long-term controlled studies with a wider range of estimated parameters are required to clarify the therapeutic potential of TOFA in this patient category. The limitation of this investigation was its open observer design pattern.Conclusion. The use of the JK inhibitor TOFA can achieve a rapid analgesic effect, inter alia due to its effect on CS and NPC.Ингибиторы янус-киназ (ЯК) блокируют внутриклеточные сигнальные пути, отвечающие за синтез провоспалительных цитокинов и медиаторов, которые, в свою очередь, вызывают активацию болевых рецепторов и развитие центральной сенситизации (ЦС). Предполагается, что ингибиторы ЯК могут быстро устранять боль и уменьшать выраженность ЦС.Цель исследования – оценить влияние ингибитора ЯК тофацитиниба (ТОФА) на выраженность боли и признаки ЦС у больных активным ревматоидным артритом (РА) через 7 и 28 дней после начала терапии.Пациенты и методы. Исследуемую группу составили 39 больных РА (средний возраст 50,9±11,1 года, 79,5% женщин), DAS28 – 5,8±0,6. Из них 89,7% были серопозитивными по ревматоидному фактору, 82,0% получали метотрексат и 18,0% – лефлуномид. Всем пациентам был назначен ТОФА 5 мг 2 раза в день в связи с неэффективностью или непереносимостью генно-инженерных биологических препаратов. Оценивались выраженность боли с помощью опросника BPI (Brief Pain Inventory), наличие невропатического компонента боли (НКБ) с помощью опросника PainDETECT и признаков ЦС с помощью опросника CSI (Central Sensitization Inventory) в первые 4 нед после назначения ТОФА.Результаты и обсуждение. Пациенты исходно испытывали умеренную или выраженную боль (в среднем 5,33±2,51 по числовой рейтинговой шкале – ЧРШ, включенной в BPI), 53,8% имели признаки ЦС (CSI ≥40), 17,9% – признаки НКБ (PainDETECT >18). Уже через 7 дней после начала приема ТОФА отмечалось статистически значимое снижение интенсивности боли в среднем до 4,06±2,2 по ЧРШ (р=0,01) и на 29,4±17,9% по оценке анальгетического эффекта терапии пациентом (BPI), а также выраженности ЦС – уменьшение значения CSI в среднем до 35,9±11,2 (р=0,01). Через 28 дней эффект усилился: наблюдалось снижение уровня боли по ЧРШ до 2,32±1,57 (р<0,001), боли по оценке анальгетического эффекта терапии пациентом до 43,6±29,6%, медианы значения PainDETECT до 2,5 [0; 8,7] (р<0,001), показателя CSI в среднем до 26,4±13,9 (р<0,001). Серьезных неблагоприятных реакций не отмечено. ТОФА обладает быстрым анальгетическим эффектом, что позволяет рассматривать его как средство выбора при проведении патогенетической терапии у больных активным РА с выраженной болью, особенно при наличии признаков ЦС и вторичной фибромиалгии. Несомненно, требуются большие по масштабу длительные контролируемые исследования с более широким кругом оцениваемых параметров для уточнения лечебного потенциала ТОФА у этой категории пациентов. Ограничением настоящего исследования явился его открытый наблюдательный характер.Заключение. Использование ингибитора ЯК ТОФА позволяет достичь быстрого анальгетического эффекта, в том числе за счет влияния на ЦС и НКБ

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

Observation of the Bc+ → J/ψπ+π0 decay

The first observation of the Bc+→J/ψπ+π0 decay is reported with high significance using proton-proton collision data, corresponding to an integrated luminosity of 9 fb−1, collected with the LHCb detector at centre-of-mass energies of 7, 8, and 13 TeV. The ratio of its branching fraction relative to the Bc+→J/ψπ+ channel is measured to beBBc+→J/ψπ+π0BBc+→J/ψπ+=2.80±0.15±0.11±0.16, where the first uncertainty is statistical, the second systematic and the third related to imprecise knowledge of the branching fractions for B+ → J/ψK*+ and Bc+→J/ψπ+ decays, which are used to determine the π0 detection efficiency. The π+π0 mass spectrum is found to be consistent with the dominance of an intermediate ρ+ contribution in accordance with a model based on QCD factorisation

RISK FOR PNEUMONIA AND TLR2 AND TLR4 GENE POLYMORPHISMS: A META-ANALYSIS

Pneumonia is one of the most common infections with high mortality rates. The gene polymorphism of Toll-like receptors that belong to the first line of defense of the immune system can make a considerable contribution to individual variability due to the risk of pneumonia. Today this issue has not been adequately explored and the data available in the literature are conflicting.Objective: to carry out a meta-analysis of the association between Toll-like receptor gene polymorphic variants and the risk of pneumonias and its coinfections.Methods. A meta-analysis was carried out to detect a possible association of the risk of pneumonia and coinfections with single nucleotide polymorphisms (SNP) in the TLR2 (rs5743708 (2258 G&gt;A; Arg753Gln) and TLR4 (rs4986790 (896A&gt;G; Asp299Gly) genes. The investigation enrolled 2312 (682 patients/1630 control individuals) and 3075 (910/2165) Caucasians for each SNP, respectively. As the rate of minor alleles of both polymorphic variants was less than 5%; the analysis was made only for a dominant genetic model.Results. Analysis of the study group showed that the A allele of TLR2 rs5743708 was associated with the risk of pneumonia (OR = 1.90; 95% CI: 1.02—3.54; P=0.042) while TLR4 rs4986790 was not associated with pneumonia. Analysis of subgroups (children/adults and community-acquired/nosocomial pneumonia) revealed no significant effects.Conclusion. The A allele of TLR2 rs5743708 may be a risk factor for susceptibility to pneumonia. These results have promises for their clinical application; however, due to the high heterogeneity and insufficient sizes of samples, these results need to be confirmed by further investigations

Prospects for the use of photodynamic method in the complex treatment of bladder cancer

Constant growth of incidence rate of bladder cancer (BC) requires refinement of methods of early diagnostics and development of efficient treatment methods. Diagnostics and adjuvant photodynamic therapy (PDT) with the use of light and photosensitizer drugs (PD) of surface transitional cell (STC) BC are not sufficiently investigated. 40 persons aged 23 - 87 suffering from STC BC took part in the research and were subjected to complex therapy (CT). STC BC patients of this group before the transurethral resection (TUR) were administered intravenously with PD, then photodynamic diagnostics (PDD) of disease focuses was performed. Control group consisted of 15 patients with BC of the same age category, for treatment of which only TUR was used. It was established that the use of CT for STC BC contributed to decrease of relapse rate and progression of disease, increase of specific survival and quality of life of patients