Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1

Quantitative analysis of dynamic computed tomography angiography for the detection of endoleaks after abdominal aorta aneurysm endovascular repair:A feasibility study

ObjectivesTo assess the feasibility of quantitative analysis of dynamic computed tomography angiography (dCTA) for the detection of endoleaks in patients who underwent endovascular repair of abdominal aortic aneurysms (EVAR).Material and methodsTwenty patients scheduled for contrast-enhanced CT angiography (CTA) of the abdominal aorta post-EVAR were prospectively enrolled. All patients received a standard triphasic CTA protocol, followed by an additional dCTA. The dCTA acquisition enabled reconstruction of color-coded maps depicting blood perfusion and a dCTA dataset of the aneurysm sac. Observers assessed the dCTA and dynamic CT perfusion (dCTP) images for the detection of endoleaks, establishing diagnostic confidence based on a modified 5-point Likert scale. An index was calculated for the ratio between the endoleak and aneurysm sac using blood flow for dCTP and Hounsfield units (HU) for dCTA. The Wilcoxon test compared the endoleak index and the diagnostic confidence of the observers.ResultsIn total, 19 patients (18 males, median age 74 years [70.5-75.7]) were included for analysis. Nine endoleaks were detected in 7 patients using triphasic CTA as the reference standard. There was complete agreement for endoleak detection between the two techniques on a per-patient basis. Both dCTA and dCTP identified an additional endoleak in one patient. The diagnostic confidence using dCTP for detection of endoleaks was not significantly superior to dCTA (5.0 [5-5] vs. 4.5 [4-5], respectively; p = 0.11); however, dCTP demonstrated superior diagnostic confidence for endoleak exclusion compared to dCTA (1.0 [1-1] vs 1.5 [1.5-1.5], respectively; p ConclusionsQuantitative analysis of dCTP imaging can aid in the detection of endoleaks and demonstrates a higher endoleak detection rate than triphasic CTA, as well as a strong correlation with visual assessment of dCTA images

Predictive Value of Cardiac CTA, Cardiac MRI, and Transthoracic Echocardiography for Cardioembolic Stroke Recurrence

Background: Transthoracic echocardiography (TTE) is the standard of care for initial evaluation of patients with suspected cardioembolic stroke. While TTE is useful for assessing certain sources of cardiac emboli, its diagnostic capability is limited in the detection of other sources, including left atrial thrombus and aortic plaques. Objectives: To investigate sensitivity, specificity and predictive value of cardiac CT angigography (cCTA), cardiac MRI (CMR), and TTE for recurrence in patients with suspected cardioembolic stroke. Methods: We retrospectively included 151 patients with suspected cardioembolic stroke who underwent TTE and either CMR (n=75) or cCTA (n=76) between January 2013 and May 2017. We evaluated for presence of left atrial thrombus, left ventricular thrombus, vulnerable aortic plaque, cardiac tumors, and valvular vegetation as causes of cardioembolic stroke. The end-point was stroke recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for recurrent stroke were calculated; the diagnostic accuracy of CMR, cCTA, and TTE was compared between and within groups using area under the curves (AUCs). Results: Twelve and 14 recurrent strokes occurred in the cCTA and CMR groups, respectively. Sensitivity, specificity, PPV and NPV were: 33.3%, 93.7%, 50.0%, and 88.2% for cCTA; 14.3%, 80.3%, 14.3%, and 80.3% for CMR; 14.3%, 83.6%, 16.7%, 80.9% for TTE in the CMR group, and 8.3%, 93.7%, 20.0% and 84.5% for TTE in the cCTA group. Accuracy was not different (p>0.05) between cCTA (0.63, 95% CI [0.49, 0.77]), CMR (0.53, [0.42, 0.63]), TTE in CMR group (0.51, [0.40, 0.61], and TTE in cCTA group (0.51, [0.42, 0.59]). In cCTA group, atrial and ventricular thrombus were detected by cCTA in 3 patients and TTE in 1 patient; in CMR group, thrombus was detected by CMR in 1 patient and TTE in 2 patients. Conclusion: cCTA, CMR, and TTE showed comparably high specificity and NPV for cardioembolic stroke recurrence. cCTA and CMR may be valid alternatives to TTE. cCTA may be preferred given potentially better detection of atrial and ventricular thrombus. Clinical impact: cCTA and CMR have similar clinical performance as TTE for predicting cardioembolic stroke recurrence. This observation may be especially important when TTE provides equivocal findings

Оптимизация параметров лазерного излучения для воздействия на пигменты на основе диоксида титана (TiO2)

В настоящее время не существует методики, позволяющей быстро и безопасно удалять татуировки и перманентный макияж, содержащие пигменты на основе диоксида титана. Тема работы является актуальной в связи с растущим спросом на такие услуги в сфере эстетической медицины, а данный пигмент является базой для широкого спектра пастельных и натуральных оттенков чернил. Объектом исследования являются дисперсные растворы диоксида титана. Целью данной работы является изучение влияния лазерного излучения на пигменты на основе диоксида титана. Полученные данные послужат основой для разработки методов удаления белых пигментов в татуировках и повысят эффективность удаления перманентного макияжа.Currently, there is no method to quickly and safely remove tattoos and permanent makeup containing titanium dioxide pigments. The topic of work is relevant in connection with the growing demand for such services in the field of aesthetic medicine, and this pigment is the base for a wide range of pastel and natural shades of ink. The object of the research are titanium dioxide dispersive solutions. The purpose of this work is to explore the effects of laser radiation on pigments based on titanium dioxide by changing its parameters. The obtained data will serve as the foundation for the development of methods for removing white pigments in tattoos and will increase the effectiveness of permanent makeup removal

Staphylococcus aureus Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils

The role of the pore-forming Staphylococcus aureus toxin Panton-Valentine leukocidin (PVL) in severe necrotizing diseases is debated due to conflicting data from epidemiological studies of community-associated methicillin-resistant S. aureus (CA-MRSA) infections and various murine disease-models. In this study, we used neutrophils isolated from different species to evaluate the cytotoxic effect of PVL in comparison to other staphylococcal cytolytic components. Furthermore, to study the impact of PVL we expressed it heterologously in a non-virulent staphylococcal species and examined pvl-positive and pvl-negative clinical isolates as well as the strain USA300 and its pvl-negative mutant. We demonstrate that PVL induces rapid activation and cell death in human and rabbit neutrophils, but not in murine or simian cells. By contrast, the phenol-soluble modulins (PSMs), a newly identified group of cytolytic staphylococcal components, lack species-specificity. In general, after phagocytosis of bacteria different pvl-positive and pvl-negative staphylococcal strains, expressing a variety of other virulence factors (such as surface proteins), induced cell death in neutrophils, which is most likely associated with the physiological clearing function of these cells. However, the release of PVL by staphylococcal strains caused rapid and premature cell death, which is different from the physiological (and programmed) cell death of neutrophils following phagocytosis and degradation of virulent bacteria. Taken together, our results question the value of infection-models in mice and non-human primates to elucidate the impact of PVL. Our data clearly demonstrate that PVL acts differentially on neutrophils of various species and suggests that PVL has an important cytotoxic role in human neutrophils, which has major implications for the pathogenesis of CA-MRSA infections

Анализ технологии предварительной подготовки нефти на месторождении "Н" (Красноярский край)

Объектом исследования является технология предварительной подготовки нефти на "Н" нефтегазоконденсатном месторождении. Целью выпускной квалификационной работы является анализ технологии предварительной подготовки нефти и подбор аппарата для отделения воды. В процессе выполнения выпускной квалификационной работы были изучены причины образования нефтяной эмульсии и способы ее разрушения; рассмотрены наиболее распространение устройства для отделения воды. Собраны данные по характеристике месторождения, составам пластовой нефти, газа и воды, технологии предварительной подготовки обводненной нефти.The object of the study is the technology of preliminary oil treatment at the" N " oil and gas condensate field. The purpose of the final qualification work is to analyze the technology of preliminary preparation of oil and the selection of a device for separating water. In the course of the final qualification work, the reasons for the formation of an oil emulsion and the methods of its destruction were studied; the most common devices for separating water were considered. Data on the characteristics of the field, the composition of reservoir oil, gas and water, and the technology of preliminary preparation of watered oil are collected