Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease

The pathophysiology of sporadic Alzheimer\u27s disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD

Efficacy and safety of left atrial appendage closure in patients with atrial fibrillation and high thromboembolic and bleeding risk

Aim. To compare the incidence of thromboembolic and hemorrhagic events after left atrial appendage occlusion (LAAO) or without prevention of thromboembolic events (TEEs) during prospective follow-up of patients with atrial fibrillation (AF) and a high risk of ischemic stroke (IS) who have contraindications to long-term anticoagulant therapy.Material and methods. The study included 134 patients with AF, a high risk of IS, and contraindications to long-term anticoagulation. Patients were divided into 2 groups as follows: the first group included patients who underwent LAAO (n=74), while the second one — those who did not undergo any TEE prevention (n=60). The follow-up period was 3 years. The cumulative rate of all-cause mortality, IS, transient ischemic attacks (TIA), and systemic embolism (SE) was taken as the primary efficacy endpoint. The primary safety endpoint included major bleeding according to GARFIELD registry criteria.Results.  The rate of composite efficacy endpoint in the LAAO group was significantly lower than in the group without thromboembolic prophylaxis (5,2 vs 17,4 per 100 patient-years; adjusted odds ratio (OR), 4,08; 95% confidence interval (CI): 1,7-9,5; p=0,001). The rate of major bleeding was comparable in both groups (2,4 in the LAAO group vs 1,3 per 100 patient-years in the group without thromboembolic prophylaxis; adjusted OR, 0,55; 95% CI: 0,1-3,09; p=0,509). In addition, the event rate of net clinical benefit (all-cause mortality + ischemic stroke/TIA/SE + major bleeding) in the LAAO group was also significantly lower (5,9 vs 18,2 per 100 patient-years; adjusted OR, 3,0; 95% CI: 1,47-6,36; p=0,003).Conclusion. Among patients with AF and contraindications to long-term anticoagulation after 3 years of follow-up, LAAO demonstrated the significant reduction of cumulative rate of all-cause mortality and non-fatal thromboembolic events. At the same time, the frequency of major bleeding was comparable between the groups, even taking into account access-site bleeding and postoperative antithrombotic therapy (ATT)-associated bleeding in the LAAO group. Further randomized clinical trials are required to confirm these data

A Spectroscopic and Photometric Study of Short-Timescale Variability in NGC5548

Results of a ground-based optical monitoring campaign on NGC5548 in June 1998 are presented. The broad-band fluxes (U,B,V), and the spectrophotometric optical continuum flux F_lambda(5100 A) monotonically decreased in flux while the broad-band R and I fluxes and the integrated emission-line fluxes of Halpha and Hbeta remained constant to within 5%. On June 22, a short continuum flare was detected in the broad band fluxes. It had an amplitude of about ~18% and it lasted only ~90 min. The broad band fluxes and the optical continuum F_lambda(5100 A) appear to vary simultaneously with the EUV variations. No reliable delay was detected for the broad optical emission lines in response to the EUVE variations. Narrow Hbeta emission features predicted as a signature of an accretion disk were not detected during this campaign. However, there is marginal evidence for a faint feature at lambda = 4962 A with FWHM=~6 A redshifted by Delta v = 1100 km/s with respect to Hbeta_narrow.Comment: 12 pages, 7 figures, accepted for publishing in A&

Prevention of Cardioembolic Complications in Patients with Atrial Fibrillation: Efficacy and Safety of Left Atrial Appendage Isolation and Oral Anticoagulants

Aim. To study the outcomes frequency and structure in patients with atrial fibrillation (AF) depending on the cardioembolic events preventing method: left atrial appendage (LAA) isolation, direct oral anticoagulants (DOACs) or warfarin.Material and methods. A prospective observational study included patients with AF and high risk of cardioembolic complications and without contraindications to anticoagulants. Patients who refused long-term oral anticoagulants taking underwent LAA isolation, the rest of the patients received DOACs or warfarin. The observation period was 3 years. Mortality, cardioembolic complications and major bleeding (according to GARFIELD criteria) cumulative incidence was assessed.Results. We included 245 patients: 46 patients were treated with LAA isolation, 100 with warfarin, and 99 with DOACs. Multivariate regression analysis demonstrated a statistically significant advantage of LAA occluder in terms of combined endpoint achieving frequency compared to warfarin (hazard ratio [HR] 3.10; 95% confidence interval [CI] 1.01-9.54; p=0.049), and to DOACs (HR 3.44, 95% CI 1.15-10.29; p=0.027). A similar result was obtained for all-cause mortality (HR 5.24; 95% CI 1.12-24.55; p=0.036 and HR 5.58; 95% CI 1.22-25.49; p=0.027, respectively). There were no significant differences in bleeding rates between the groups.Conclusion. This observational study demonstrates the superiority of LAA isolation as a first-line therapy over DOACs and warfarin in patients with AF and high risk of cardioembolic complications. Randomized trials are required to confirm these observations

Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XVI. A Thirteen-Year Study of Spectral Variability in NGC 5548

We present the final installment of an intensive 13-year study of variations of the optical continuum and broad H-beta emission line in the Seyfert 1 galaxy NGC 5548. The data base consists of 1530 optical continuum measurements and 1248 H-beta measurements. The H-beta variations follow the continuum variations closely, with a typical time delay of about 20 days. However, a year-by-year analysis shows that the magnitude of emission-line time delay is correlated with the mean continuum flux. We argue that the data are consistent with the simple model prediction that the size of the broad-line region is proportional to the square root of the ionizing luminosity. Moreover, the apparently linear nature of the correlation between the H-beta response time and the nonstellar optical continuum arises as a consequence of the changing shape of the continuum as it varies, specifically with the optical (5100 A) continuum luminosity proportional to the ultraviolet (1350 A) continuum luminosity to the 0.56 power.Comment: 20 pages plus 4 figures. Accepted for publication in The Astrophysical Journa

Study of the structure and kinematics of the NGC 7465/64/63 triplet galaxies

This paper is devoted to the analysis of new observational data for the group of galaxies NGC 7465/64/63, which were obtained at the 6-m telescope of the Special Astrophysical Observatory of the Russian Academy of Sciences (SAO RAS) with the multimode instrument SCORPIO and the Multi Pupil Fiber Spectrograph. For one of group members (NGC 7465) the presence of a polar ring was suspected. Large-scale brightness distributions, velocity and velocity dispersion fields of the ionized gas for all three galaxies as well as line-of-sight velocity curves on the basis of emission and absorption lines and a stellar velocity field in the central region for NGC 7465 were constructed. As a result of the analysis of the obtained information, we revealed an inner stellar disk (r ~ 0.5 kpc) and a warped gaseous disk in addition to the main stellar disk, in NGC 7465. On the basis of the joint study of photometric and spectral data it was ascertained that NGC 7464 is the irregular galaxy of the IrrI type, whose structural and kinematic peculiarities resulted most likely from the gravitational interaction with NGC 7465. The velocity field of the ionized gas of NGC 7463 turned out typical for spiral galaxies with a bar, and the bending of outer parts of its disk could arise owing to the close encounter with one of galaxies of the environment.Comment: 20 pages, 6 figure

2D Spectroscopy of Candidate Polar-Ring Galaxies: I. The Pair of Galaxies UGC 5600/09

Observations of the pair of galaxies VV 330 with the SCORPIO multimode instrument on the 6-m Special Astrophysical Observatory telescope are presented. Large-scale velocity fields of the ionized gas in H-alfa and brightness distributions in continuum and H-alfa have been constructed for both galaxies with the help of a scanning Fabry Perot interferometer. Long-slit spectroscopy is used to study the stellar kinematics. Analysis of the data obtained has revealed a complex structure in each of the pair components. Three kinematic subsystems have been identified in UGC 5600: a stellar disk, an inner gas ring turned with respect to the disk through ~80degrees, and an outer gas disk. The stellar and outer gas disks are noncoplanar. Possible scenarios for the formation of the observed multicomponent kinematic galactic structure are considered, including the case where the large-scale velocity field of the gas is represented by the kinematic model of a disk with a warp. The velocity field in the second galaxy of the pair, UGC 5609, is more regular. A joint analysis of the data on the photometric structure and the velocity field has shown that this is probably a late-type spiral galaxy whose shape is distorted by the gravitational interaction, possibly, with UGC 5600.Comment: 18 pages, 6 figure

Applicant perspectives during selection

We provide a comprehensive but critical review of research on applicant reactions to selection procedures published since 2000 (n = 145), when the last major review article on applicant reactions appeared in the Journal of Management. We start by addressing the main criticisms levied against the field to determine whether applicant reactions matter to individuals and employers (“So what?”). This is followed by a consideration of “What’s new?” by conducting a comprehensive and detailed review of applicant reaction research centered upon four areas of growth: expansion of the theoretical lens, incorporation of new technology in the selection arena, internationalization of applicant reactions research, and emerging boundary conditions. Our final section focuses on “Where to next?” and offers an updated and integrated conceptual model of applicant reactions, four key challenges, and eight specific future research questions. Our conclusion is that the field demonstrates stronger research designs, with studies incorporating greater control, broader constructs, and multiple time points. There is also solid evidence that applicant reactions have significant and meaningful effects on attitudes, intentions, and behaviors. At the same time, we identify some remaining gaps in the literature and a number of critical questions that remain to be explored, particularly in light of technological and societal changes

Сравнение вариантов анестезиологического обеспечения имплантации окклюдера ушка левого предсердия у пациентов с фибрилляцией предсердий

Objective: comparison of general anesthesia (GA) and intravenous conscious sedation during left atrial appendage occlusion (LAAO).Materials and Methods. The study included 120 patients from LAAO Register at the National Medical Research Center of Cardiology, who were divided into GA (n = 100) and intravenous sedation (n = 20) groups. In-hospital outcomes were assessed, as well as outcomes and data of transesophageal echocardiography (TEE) at 45 days and 6 months.Results. 3 patients required intraoperative conversion of the anesthetic method to GA. The duration of the procedure, the time of fluoroscopy, the amount of contrast medium, and the technical success did not differ signifcantly between the two groups. The incidence of in-hospital complications in the GA group was 10%, and 15% in the intravenous sedation group (p = 0.453). There were no statistically signifcant differences between the groups in long-term outcomes and TEE data after 45 days and 6 months.Conclusion. Combined intravenous sedation with local anesthesia is an effective and fairly safe method of anesthesiological support for implantation of the occluder of the left atrial auricle. It can be used in patients with a high risk of GA, with predictable difculties of tracheal intubation, as well as if the patient wishes accordingly. The limitations of the use of intravenous sedation in combination with local anesthesia are anatomical variants of SFM that are difcult for occluder implantation, as well as the patient's low tolerance to ECG in consciousness.Цель: сравнение вариантов анестезиологического обеспечения – общей анестезии (ОА) и внутривенной седации при имплантации окклюдера ушка левого предсердия (УЛП).Материалы и методы. В исследование включено 120 пациентов из регистра имплантации окклюдеров УЛП НМИЦ кардиологии, которые разделены на две группы с учетом использованной тактики анестезиологического обеспечения: ОА (n = 100) и внутривенной седации (n = 20). Оценивали внутригоспитальные исходы, а также исходы и данные чреспищеводной эхокардиографии (ЧПЭхоКГ) через 45 дней и 6 мес.Результаты: 3 пациентам понадобилась интраоперационная конверсия метода анестезии. Длительность процедуры, время флюороскопии, количество контраста, технический успех статистически значимо не различались между двумя группами. Частота внутригоспитальных осложнений в группе ОА составила 10%, а в группе внутривенной седации – 15% (p = 0,453). При оценке отдаленных исходов через 45 дней и 6 мес. статистически значимых различий между группами не выявлялось.Заключение. Сочетанная внутривенная седация с местной анестезией является эффективной и достаточно безопасной методикой анестезиологического обеспечения имплантации окклюдера УЛП. Ее можно применять у пациентов с высоким риском ОА, при предсказуемых трудностях интубации трахеи, а также при соответствующем желании пациента. Ограничениями применения внутривенной седации в сочетании с местной анестезией являются трудные для имплантации окклюдера анатомические варианты УЛП, а также низкая толерантность пациента к ЧПЭхоКГ в сознании

СЛУЧАЙ РАЗВИТИЯ ИНТРАМУРАЛЬНОЙ ГЕМАТОМЫ ЛЕВОГО ПРЕДСЕРДИЯ ПОСЛЕ ПРОВЕДЕНИЯ ЧРЕСКОЖНОГО КОРОНАРНОГО ВМЕШАТЕЛЬСТВА

Left atrial Intramural hematoma (LAIH) is rare complication cardiac invasive procedures. The article analyses the mechanism of formation of this pathology. The case of the LAIH after percutaneous coronary intervention (PCI) is presented. The patient complained of intensive chest pain. When performing ECHO, LAIH was found. LAIH occupied a large part of the cavity left atrium. The conservative supervision of the patient was chosen despite the compession of the left inferior pulmonary vein and symptoms of the acute heart failure. The successful symptomatic treatment was conducted. Taking into consideration the recent PCI dual antiplatelet therapy was not interrupted. LAIH gradually regressed. Five weeks after the desease began, the patient was discharged from the hospital. Nine months after almost full lysis of LAIH was observed. The discussion section is devoted to the issues of diagnosis, the choice of medical tactics, the necessity of surgical treatment and the stop of antitrombotic theatment.Интрамуральная гематома левого предсердия (ИГЛП) – редко встречающееся осложнение вмешательств на сердце. В статье рассматриваются механизмы формирования этой патологии. Представлен случай развития ИГЛП после проведения чрескожного коронарного вмешательства (ЧКВ). По окончании процедуры больной пожаловался на интенсивные боли в груди. При проведении ЭхоКГ выявлена ИГЛП, занимающая большую часть полости левого предсердия (ЛП). Несмотря на компрессию левой нижней легочной вены и симптомы острой сердечной недостаточности, была выбрана консервативная тактика ведения, проводилось успешное симптоматическое лечение. Учитывая недавнее ЧКВ, двойная дезагрегантная терапия не прерывалась. ИГЛП постепенно уменьшалась в размерах. Через пять недель от начала заболевания пациент был выписан из стационара, через девять месяцев наблюдался практически полный лизис ИГЛП. Раздел обсуждения посвящен вопросам диагностики, выбора лечебной тактики, целесообразности проведения хирургического лечения и отмены антитромботической терапии