Microbial landscape microflora of lower respiratory ways in HIV-infected patients

The article describes the structure and dynamics of microflora in HIV-infected patients, occurring in the territory of Perm and the Perm region in the period from 2014 to 2018.В статье рассмотрена структура и динамика микрофлоры у ВИЧ-инфицированных пациентов, встречающаяся на территории Перми и Пермского края в период с 2014 по 2018 год

High-resolution ptychographic imaging at a seeded free-electron laser source using OAM beams

Electromagnetic waves possessing orbital angular momentum (OAM) are powerful tools for applications in optical communications, new quantum technologies and optical tweezers. Recently, they have attracted growing interest since they can be harnessed to detect peculiar helical dichroic effects in chiral molecular media and in magnetic nanostructures. In this work, we perform single-shot per position ptychography on a nanostructured object at a seeded free-electron laser, using extreme ultraviolet OAM beams of different topological charge order $\ell$ generated with spiral zone plates. By controlling $\ell$, we demonstrate how the structural features of OAM beam profile determine an improvement of about 30% in image resolution with respect to conventional Gaussian beam illumination. This result extends the capabilities of coherent diffraction imaging techniques, and paves the way for achieving time-resolved high-resolution (below 100 nm) microscopy on large area samples.Comment: M. Pancaldi and F. Guzzi contributed equally to this wor

Содержание фактора активации тромбоцитов в плазме крови больных бронхиальной астмой. Влияние тромбоцитафереза

Levels of serum PA F were investigated in patients with various bronchial asthma (BA) forms and in various forms of the clinical manifestation of the disease before and after plateletapheresis (PtA). 15 patients with BA (9 atopic and 6 aspirin-sensitive ones) and 4 healthy donors were examined. The examination demonstrated that only tracks of PA F in the healthy donors are registered but in BA patients the PAF levels were significantly increased. It was found, that in patients with atopic BA the PAF levels were almost by two times higher than in aspirinic BA ones. Moreover, the PAF level in a great extent depends on the disease degree. The serum PAF level was decreased in 42% in average after trobmocytapheresis.The study demonstrates the features of thrombocytapheresis action and develops the imagination about its action mechanisms.Исследовался уровень фактора активации тромбоцитов (ФАТ) в крови больных различными формами бронхиальной астмы разной степени тяжести и влияние тромбоцитафереза на этот показатель. Обследовано 15 больных с БА (9 с атопической и 6 с аспириновой) и 4 здоровых донора. Исследования показали, что в крови здоровых доноров регистрируются лишь следы ФАТ, тогда как у больных БА содержание ФАТ значительно повышено. Выявлено, что у больных аспириновой астмой уровень ФАТ почти в 2 раза ниже, чем в группе больных атопической астмой. Кроме того, чем тяж елее протекает заболевание, тем вы ш е уровень ФАТ. После тромбоцитафереза уровень ФАТ в крови больных, получавших данную терапию , снизился в среднем на 42%.Исследования раскрывают особенности действия тромбоцитафереза, углубляют представления о механизме действия этой процедуры

СЕМЕЙНЫЙ ГЕМОФАГОЦИТАРНЫЙ ЛИМФОГИСТИОЦИТОЗ

Family hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) is a rare hereditary disease, which is based on a disturbance of the regulation of the immune response, leading to proliferation and activation of histiocytes, phagocytosis of peripheral blood cells. The most common mutations include – PRF1, UNC13D, STX11. Two cases of familial hemophagocytic lymphogystyocytosis in children of an early age from a single family, features of the course are described.Семейный гемофагоцитарный лимфогистиоцитоз (гемофагоцитарный синдром) – редкое наследственное заболевание, в основе которого лежит нарушение регуляции иммунного ответа, приводящее к пролиферации и активации гистиоцитов, фагоцитозу клеток периферической крови. К наиболее частым мутациям относят PRF1, UNC13D и STX11. Данное заболевание необходимо учитывать в дифференциальной диагностике сложных инфекционных болезней у детей. Представлены два случая семейного гемофагоцитарного лимфогистиоцитоза у детей раннего возраста из одной семьи и обзор литературы

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL)

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC

Mono-, bi-, and tri-metallic Ni-based catalysts for the catalytic hydrotreatment of pyrolysis liquids

Catalytic hydrotreatment is a promising technology to convert pyrolysis liquids into intermediates with improved properties. Here, we report a catalyst screening study on the catalytic hydrotreatment of pyrolysis liquids using bi- and tri-metallic nickel-based catalysts in a batch autoclave (initial hydrogen pressure of 140 bar, 350 A degrees C, 4 h). The catalysts are characterized by a high nickel metal loading (41 to 57 wt%), promoted by Cu, Pd, Mo, and/or combination thereof, in a SiO2, SiO2-ZrO2, or SiO2-Al2O3 matrix. The hydrotreatment results were compared with a benchmark Ru/C catalyst. The results revealed that the monometallic Ni catalyst is the least active and that particularly the use of Mo as the promoter is favored when considering activity and product properties. For Mo promotion, a product oil with improved properties viz. the highest H/C molar ratio and the lowest coking tendency was obtained. A drawback when using Mo as the promoter is the relatively high methane yield, which is close to that for Ru/C. H-1, C-13-NMR, heteronuclear single quantum coherence (HSQC), and two-dimensional gas chromatography (GC x GC) of the product oils reveal that representative component classes of the sugar fraction of pyrolysis liquids like carbonyl compounds (aldehydes and ketones and carbohydrates) are converted to a large extent. The pyrolytic lignin fraction is less reactive, though some degree of hydrocracking is observed

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Легочные осложнения у детей и подростков после трансплантации гемопоэтических стволовых клеток

Relevance. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) makes it possible to treat severe malignant and non-malignant hematopoietic disorders system. Pulmonary complications (PC) occur in 40–60 % of patients after allo-HSCT. However to date, the effect of HSCT on functional and morphological pulmonary changes in recipients remains insufficiently studied.The objective of current study was to evaluate risk factors affecting long-term survival in children and adolescents after allo-HSCT.Methods and materials. The current study was both retrospective and prospective. The analysis included 362 patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), aged 5 months to 18 years, who received allo-HSCT at Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in 2000–2018. All the patients underwent chest computed tomography (CT). When detecting CT changes, we performed fibrobronchoscopy (FBS) with microbiological examination of bronchoalveolar lavage (BAL).Results. PC were diagnosed in 124 patients (64 %) who received allo-HSCT in 2014–2018. Decrease of overall survival (OS) is associated with PC development during the first year after allo-HSCT(р<0,001).The development of early PC in remission of the underlying disease significantly affected OS (p=0.001).The probability of PC development is 2.26 times higher in patients older than 9 years (p=0.006). When comparing the intensity of conditioning regimens (MACvsRIC) in remission of the underlying disease, we did not get significant differences in the incidence of PC (p>0.05). Graft source, donor type, HLA-compatibility, recipient gender did not affect the incidence of PC (p>0.05). When using graft-versus-host disease (GVHD) prophylaxis (ptCYvsATG), the 5-year OS in patients without PC was 78.8 % and 62.8 %respectively. The 5-year OS in patients with PC was 51.8 % and 42.4 % respectively (р=0.007). Decrease of OS in patients with PC is associated with chGVHD(58.3 %,) (р=0.03).Conclusion. Pulmonary complications (infectious and non-infectious) in allo-HSCT recipients are more likely to occur in the first year after transplantation. Among bacterial pathogens, the predominance of Gr(-) flora remains. The incidence of pulmonary complications was significantly lower when using ptCY as a prevention of GVHD. Введение. Аллогенная трансплантация гемопоэтических стволовых клеток (алло-ТГСК) позволяет излечить тяжелые злокачественные и незлокачественные заболевания системы крови. Легочные осложнения (ЛО) после алло-ТГСК встречаются у 40–60% пациентов. Однако до настоящего времени остается недостаточно изученным влияние ТГСК на функциональные и морфологические изменения в легких у реципиентов.Цель – изучить факторы риска, влияющие на долгосрочную выживаемость у детей и подростков после алло-ТГСК.Методы и материалы. Настоящее исследование было как ретроспективным, так и проспективным. В анализ включены 362 пациента с острым лимфобластным лейкозом (ОЛЛ) и острым миелоидным лейкозом (ОМЛ), в возрасте от 5 месяцев до 18 лет, получивших алло-ТГСК в НИИ ДОГиТ им. Р. М. Горбачёвой в период с 2000 по 2018 г. Всем пациентам проводилась компьютерная томография (КТ) грудной клетки. При обнаружении изменений на КТ мы выполняли диагностическую фибробронхоскопию (ФБС) с микробиологическим исследованием бронхоальвеолярного лаважа (БАЛ). Результаты. ЛО диагностированы у 124 (64 %) пациентов из 193 пациентов, получавших алло-ТГСК с 2014 по 2018 г. Снижение общей выживаемости (ОВ) ассоциировано с развитием ЛО в течение первого года после алло-ТГСК (р<0,001). Развитие ранних легочных осложнений в ремиссии основного заболевания значимо влияло на ОВ (р=0,001). Шанс развития ЛО в 2,26 раза выше у пациентов старше 9 лет (р=0,006). При сравнении интенсивности режимов кондиционирования (миелоаблативные (МАК) режимы и режимы со сниженной интенсивностью доз (РИК)) в ремиссии основного заболевания нами не было получено значимых различий в частоте возникновения легочных осложнений (р>0,05). Источник трансплантата, тип донора, совместимость по генам HLA-системы, пол реципиента не оказывали влияния на частоту развития легочных осложнений (р>0,05). При использовании режима профилактики реакции «трансплантат против хозяина» (РТПХ) (птЦФ против АТГ) 5-летняя ОВ у пациентов без ЛО составила 78,8 и 62,8 % соответственно. У пациентов с ЛО 5-летняя ОВ – 51,8 и 42,4 % соответственно (р=0,007). Ухудшение общей выживаемости у пациентов с ЛО ассоциировано с хРТПХ (58,3 %) (р=0,03).Заключение. Легочные осложнения (инфекционные и неинфекционные) у реципиентов алло-ТГСК чаще возникают в первый год после выполнения трансплантации. Среди бактериальных возбудителей сохраняется преобладание Гр(-)-флоры. Частота развития легочных осложнений была значительно ниже при использовании птЦФ в качестве профилактики РТПХ.