Cardiac-respiratory self-gated cine ultra-short echo time (UTE) cardiovascular magnetic resonance for assessment of functional cardiac parameters at high magnetic fields

Background: To overcome flow and electrocardiogram-trigger artifacts in cardiovascular magnetic resonance (CMR), we have implemented a cardiac and respiratory self-gated cine ultra-short echo time (UTE) sequence. We have assessed its performance in healthy mice by comparing the results with those obtained with a self-gated cine fast low angle shot (FLASH) sequence and with echocardiography. Methods: 2D self-gated cine UTE (TE/TR = 314 μs/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 5 min 5 sec) and self-gated cine FLASH (TE/TR = 3 ms/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 4 min 49 sec) images were acquired at 9.4 T. Volume of the left and right ventricular (LV, RV) myocardium as well as the end-diastolic and -systolic volume was segmented manually in MR images and myocardial mass, stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were determined. Statistical differences were analyzed by using Student t test and Bland-Altman analyses. Results: Self-gated cine UTE provided high quality images with high contrast-to-noise ratio (CNR) also for the RV myocardium (CNRblood-myocardium = 25.5 ± 7.8). Compared to cine FLASH, susceptibility, motion, and flow artifacts were considerably reduced due to the short TE of 314 μs. The aortic valve was clearly discernible over the entire cardiac cycle. Myocardial mass, SV, EF and CO determined by self-gated UTE were identical to the values measured with self-gated FLASH and showed good agreement to the results obtained by echocardiography. Conclusions: Self-gated UTE allows for robust measurement of cardiac parameters of diagnostic interest. Image quality is superior to self-gated FLASH, rendering the method a powerful alternative for the assessment of cardiac function at high magnetic fields.</p

Оценка негосударственной поддержки малого и среднего бизнеса как фактора конкурентоспособности компании (на примере стран Таможенного союза)

Объектом исследования является деятельность торгово-промышленной палаты в России и в странах Таможенного союза ЕАЭС. Предметом исследования являются возможности торгово-промышленной палаты в России и в странах Таможенного союза ЕАЭС. Цель работы – обосновать, что негосударственная поддержка является фактором конкурентоспособности предприятий малого и среднего бизнеса в странах Таможенного союза ЕАЭС. Актуальность работы обусловлена значимостью торгово-промышленной палаты в развитии, как национальной экономики, так и достижении конкурентоспособности предприятий МСБ – участников внешнеэкономической деятельности.The object of research is the activity of the Chamber of Commerce and Industry of the Russian Federation and the countries of the Eurasian Economic Union. The subject of research is opportunities of Chamber of Commerce and Industry of the Russian Federation and the countries of the Eurasian Economic Union. The purpose of work - to prove that the non-governmental support is a factor in the competitiveness of small and medium-sized businesses in the countries of the Eurasian Economic Union. Timeliness of the work is due to the significance of the Chamber of Commerce and Industry in the development of business, as the national economy and achieving competitiveness of SMEs - participants of international economic activity

Transthoracic echocardiography reference values in juvenile and adult 129/Sv mice

Background In the recent years, the use of Doppler-echocardiography has become a standard non-invasive technique in the analysis of cardiac malformations in genetically modified mice. Therefore, normal values have to be established for the most commonly used inbred strains in whose genetic background those mutations are generated. Here we provide reference values for transthoracic echocardiography measurements in juvenile (3 weeks) and adult (8 weeks) 129/Sv mice. Methods Echocardiographic measurements were performed using B-mode, M-mode and Doppler-mode in 15 juvenile (3 weeks) and 15 adult (8 weeks) mice, during isoflurane anesthesia. M-mode measurements variability of left ventricle (LV) was determined. Results Several echocardiographic measurements significantly differ between juvenile and adult mice. Most of these measurements are related with cardiac dimensions. All B-mode measurements were different between juveniles and adults (higher in the adults), except for fractional area change (FAC). Ejection fraction (EF) and fractional shortening (FS), calculated from M-mode parameters, do not differ between juvenile and adult mice. Stroke volume (SV) and cardiac output (CO) were significantly different between juvenile and adult mice. SV was 31.93 ± 8.67 μl in juveniles vs 70.61 ± 24.66 μl in adults, ρ < 0.001. CO was 12.06 ± 4.05 ml/min in juveniles vs 29.71 ± 10.13 ml/min in adults, ρ < 0.001. No difference was found in mitral valve (MV) and tricuspid valve (TV) related parameters between juvenile and adult mice. It was demonstrated that variability of M-mode measurements of LV is minimal. Conclusions This study suggests that differences in cardiac dimensions, as wells as in pulmonary and aorta outflow parameters, were found between juvenile and adult mice. However, mitral and tricuspid inflow parameters seem to be similar between 3 weeks and 8 weeks mice. The reference values established in this study would contribute as a basis to future studies in post-natal cardiovascular development and diagnosing cardiovascular disorders in genetically modified mouse mutant lines.Peer Reviewe

Опыт ведения пациентов с болезнью Фабри после изменения дозы или смены препарата в процессе проведения ферментозаместительной терапии

В связи с перебоями в поставках агалсидазы бета в 2009 г. многие пациенты с болезнью Фабри (БФ) были переведены на терапию меньшими дозами этого фермента или на лечение другим ферментом – агалсидазой альфа. В настоящем наблюдательном исследовании проведена оценка изменения состояния «таргетных» органов и симптомов, возникающих вследствие снижения доз или смены препарата на агалсидазу альфа. Под наблюдением находились 105 взрослых пациентов с БФ, получавшие агалсидазу бета (в дозе 1 мг / кг массы тела) в течение 1 года и более, которые были неслучайным образом разделены на тех, кто продолжил лечение по данной схеме (группа обычных доз, n = 38), тех, кому доза была снижена до 0,3–0,5 мг / кг (группа сниженных доз, n = 29), и тех, которые были переведены на лечение агалсидазой альфа в дозе 0,2 мг / кг (группа смены фермента), с последующим проспективным наблюдением в течение 1 года. Оценивались клинические события (смерть, инфаркт миокарда, тяжелая аритмия, инсульт, прогрессирование до терминальной стадии почечной недостаточности); изменения функции сердца и почек, неврологический статус и симптомы, связанные с БФ (невропатическая боль, гипогидроз, диарея и тяжесть заболевания). В группе обычных доз функциональное состояние органов и симптомы, связанные с БФ, оставались стабильными. В группе ниженных доз отмечено уменьшение рассчитанной скорости клубочковой фильтрации примерно на 3 мл / мин / 1,73 м2 (p = 0,01), а в группе смены препарата – повышение медианного соотношения альбумин / креатинин со 114 (0–606) мг / г до 216 (0–2062) мг / г (p = 0,03). Кроме того, в группах сниженных доз и смены препарата обнаруживалось существенное повышение средних оценок по индексу оценки тяжести Майнц и частоты приступов боли, хронической боли, боли в желудочно-кишечном тракте и диареи. У пациентов, получавших агалсидазу бета в обычных дозах, наблюдали стабильное течение болезни, в то время как снижение доз привело к ухудшению функции почек и усугублению симптомов. Переход на агалсидазу альфа безопасен, однако возможны прогрессирование микроальбуминурии и усиление выраженности симптомов БФ

Heart rate monitoring on the stroke unit. What does heart beat tell about prognosis? An observational study

<p>Abstract</p> <p>Background</p> <p>Guidelines recommend maintaining the heart rate (HR) of acute stroke patients within physiological limits; data on the frequency and predictors of significant deviations from these limits are scarce.</p> <p>Methods</p> <p>Demographical data, stroke risk factors, NIH stroke scale score, lesion size and location, and ECG parameters were prospectively assessed in 256 patients with ischemic stroke. Patients were continuously monitored for at least 24 hours on a certified stroke unit. Tachycardia (HR ≥120 bpm) and bradycardia (HR <45 bpm) and cardiac rhythm (sinus rhythm or atrial fibrillation) were documented. We investigated the influence of risk factors on HR disturbances and their respective influence on dependence (modified Rankin Scale ≥ 3 after three months) and mortality.</p> <p>Results</p> <p>HR ≥120 bpm occurred in 39 patients (15%). Stroke severity (larger lesion size/higher NIHSS-score on admission), atrial fibrillation and HR on admission predicted its occurrence. HR <45 bpm occurred in 12 patients (5%) and was predicted by lower HR on admission. Neither HR ≥120 nor HR <45 bpm independently predicted poor outcome at three moths. Stroke location had no effect on the occurrence of HR violations. Clinical severity and age remained the only consistent predictors of poor outcome.</p> <p>Conclusions</p> <p>Significant tachycardia and bradycardia are frequent phenomena in acute stroke; however they do not independently predict clinical course or outcome. Continuous monitoring allows detecting rhythm disturbances in stroke patients and allows deciding whether urgent medical treatment is necessary.</p

Lysosomal protease deficiency or substrate overload induces an oxidative-stress mediated STAT3-dependent pathway of lysosomal homeostasis

How cells regulate their lysosomal proteolytic capacity is only partly understood. Here, the authors show that lysosomal protease deficiency or substrate overload induces lysosomal stress leading to activation of a STAT3-dependent, TFEB-independent pathway of lysosomal hydrolase expression

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

Previous analysis of the Cerberus like 2 knockout (Cerl2(-/-)) mouse revealed a significant mortality during the first day after birth, mostly due to cardiac defects apparently associated with randomization of the left-right axis. We have however, identified Cerl2-associated cardiac defects, particularly a large increase in the left ventricular myocardial wall in neonates that cannot be explained by laterality abnormalities. Therefore, in order to access the endogenous role of Cerl2 in cardiogenesis, we analyzed the embryonic and neonatal hearts of Cerl2 null mutants that did not display a laterality phenotype. Neonatal mutants obtained from the compound mouse line Cer2(-/-)Fundacao para a Ciencia e Tecnologia (FCT); IBB/CBME [PEst-OE/EQB/LA0023/2011]; FCT [SFRH/BD/62081/2009]info:eu-repo/semantics/publishedVersio

Sex-specific pathways in early cardiac response to pressure overload in mice

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF