Non-classical Indications for Cardiac Resynchronization Therapy

Based on randomized controlled studies, cardiac resynchronization therapy (CRT) is currently indicated in patients with systolic heart failure of New York Heart Association (NYHA) functional class III and IV, left ventricular ejection fraction < 35% and wide QRS (>120 ms). Most of the enrolled patients were in sinus rhythm, were not previously paced and had mainly LBBB. Thus, there are uncertainties regarding several other populations, not included or underrepresented in the main studies. These populations include patients with atrial fibrillation (AF), previous pacemakers considered for upgrade to CRT, RBBB, narrow QRS < 120 ms, NYHA functional class <III, or right heart failure. These non-classical indications are herein reviewed.             Although CRT seems to benefit patients with AF and patients with preexisting pacemakers, in patients with NYHA functional class II-III, or with narrow QRS, or with RBBB, or in those with predominant right heart failure, the role of CRT is not established yet and further relevant clinical trials are needed

Projektiranje i analiza digitalnog sata

Sat je jedan od najstarijih ljudskih otkrića. U principu, potrebno je znati osnovne fizičke procese koji se ponavljaju s određenom učestalošću, i način da se izmjeri koliko taj proces traje. Kao što se godišnja doba i faze mjeseca mogu iskoristiti za mjerenje protoka određenih dužih perioda vremena, tako se i kraći periodi mogu koristiti za mjerenje sati i minuta. Sunčani sat koji mjeri vrijeme dana pomoću smjera sjenke koju baca određeni predmet osvjetljen suncem, bio je dobro poznat u drevnim vremenima. Pješčani satovi mjerili su vrijeme prolaskom sitnog pijeska kroz uzani otvor na staklenoj posudi. Razvoj elektronike u 20. stoljeću doveo je do satova bez ikakvog mehanizma. Vrijeme na ovakvim satovima mjerilo se na razne načine, na primjer pomoću kvarcnih kristala ili raspadanjem radioaktivnih elemenata. Čak su i mehanički satovi napajani baterijama, čime je navijanje sata postalo suvišno. Cilj ovog rada je projektirati i analizirati jedan digitalni zidni sat s integriranim krugom Maxim IC type DS3231 koji je kvalificiran od strane proizvođača kao „iznimno točan I2C sat u stvarnom vremenu (RTC), s integriranim temperaturno kompenziranim kristalnim oscilatorom (TCXO) i kristalom.“[1] Smatra se da integracija kristalnog rezonatora povećava dugotrajnu točnost uređaja, garantirajući maksimalnu pogrešku manju od 64 sekunde u godini, i temperaturni opseg od 0 do 40 °C (32 do 104 °F). Uređaj uključuje baterijski ulaz koji održava rad uređaja u odsutnosti vanjskog izvora.Clock is one of the oldest human inventions. In principle, it is necessary to know basic physical processes which are repeated with a certain frequency and method to measure how much this process lasts. Such as the season and phase of the month can be used to measure flow of certain lengthy periods of time, so are shorter periods used to measure hours and minutes. A sunidial shows the time by displaying the position of shadow on flat surface. Hourglasses measured time by passing of the fine sand through narrow opening on a glass container. The objective of this article is to project and analyze digital wall clock with Maxim IC type DS3231, qualified by its manufacturer as an „extremely accurate I2C real time clock (RTC) with integrated temperature compensated crystal oscillator (TCXO) and crystal.“ It is considered that integration of the crystal resonator enhances the long-term accuracy of derive, guaranteeing a maximum error of less than 64 seconds over a year, and over a temperature range 0 to 40 °C (32 to 104 °F). The device incorporates a battery input which maintains running of the device in the absence of external power

Теоретические основы интенсификации работы грануляционных устройств с усовершенствованной гидродинамикой

Одним із способів зменшення габаритів грануляційного обладнання є вдосконалення гідродинамічних умов перебування в ньому дисперсної фази. Цього можна досягти, зокрема, за рахунок застосування вихрових і високотурбулізованних потоків. Представлена робота присвячена обґрунтуванню можливості створення алгоритму управління рухом дисперсної фази в робочому просторі грануляційного пристрою, на підставі якого буде визначена його оптимальна конструкція з мінімальними габаритами.Одним из способов уменьшения габаритов грануляционного оборудования является усовершенствование гидродинамических условий пребывания в нём дисперсной фазы. Этого можно достичь, в частности, за счет применения вихревых и высокотурбулизованных потоков. Представленная работа посвящена обоснованию возможности создания алгоритма управления движением дисперсной фазы в рабочем пространстве грануляционного устройства, на основании которого будет определена его оптимальная конструкция с минимальными габаритами

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel® macrocarriers

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel® macrocarriers in fixed-bed BioBLU®320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms

Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction

Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice

Role of CsrR, Hyaluronic Acid, and SpeB in the Internalization of Streptococcus pyogenes M Type 3 Strain by Epithelial Cells

Internalization of group A streptococcus by human epithelial cells has been extensively studied during the past 6 years. It is now clear that multiple mechanisms are involved in this process. We have previously demonstrated that the CsrR global regulator controls the internalization of an invasive M type 3 strain through regulation of the has (hyaluronic acid synthesis) operon, as well as another, unknown gene(s). Recently, it was reported that the CsrR-regulated cysteine protease (SpeB) is also involved in bacterial uptake. In this study we have examined the roles of CsrR, hyaluronic acid capsule, and SpeB in streptococcal internalization. We have constructed isogenic mutants of the M3 serotype deficient in the csrR, hasA, and speB genes and tested their ability to be internalized by HEp-2 epithelial cells. Inactivation of csrR abolished internalization, while inactivation of either hasA or speB increased the internalization efficiency. Mutation in csrR derepressed hasA transcription and lowered the activity of SpeB, while no effect on speB transcription was observed. The speB mutant expressed smaller amounts of capsule, while the hasA mutant transcribed more csrR and speB mRNAs. Thus, it seems that complex interactions between CsrR, SpeB, and capsule are involved in modulation of group A streptococcus internalization