Perfil sócio-econômico e tecnológico das propriedades viticolas dos municípios de Bento Gonçalves e Flores da Cunha - RS.

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Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.

Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and against Plasmodium berghei in infected mice. With respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. Concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initially oxidized at the benzylic chain to benzoyl naphthoquinones in a heme-catalyzed reaction within the digestive acidic vesicles of the parasite. The major putative benzoyl metabolites were then found to function as redox cyclers: (i) in their oxidized form, the benzoyl metabolites are reduced by NADPH in glutathione reductase-catalyzed reactions within the cytosols of infected red blood cells; (ii) in their reduced forms, these benzoyl metabolites can convert methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Studies on a fluorinated suicide-substrate indicate as well that the glutathione reductase-catalyzed bioactivation of naphthoquinones is essential for the observed antimalarial activity. In conclusion, the antimalarial naphthoquinones are suggested to perturb the major redox equilibria of the targeted infected red blood cells, which might be removed by macrophages. This results in development arrest and death of the malaria parasite at the trophozoite stage

Computational and experimental analysis identified 6-diazo-5-oxonorleucine as a potential agent for treating infection by Plasmodium falciparum

Plasmodium falciparum (PF) is the most severe malaria parasite. It is developing resistance quickly to existing drugs making it indispensable to discover new drugs. Effective drugs have been discovered targeting metabolic enzymes of the parasite. In order to predict new drug targets, computational methods can be used employing database information of metabolism. Using this data, we performed recently a computational network analysis of metabolism of PF. We analyzed the topology of the network to find reactions which are sensitive against perturbations, i.e., when a single enzyme is blocked by drugs. We now used a refined network comprising also the host enzymes which led to a refined set of the five targets glutamyl–tRNA (gln) amidotransferase, hydroxyethylthiazole kinase, deoxyribose–phophate aldolase, pseudouridylate synthase, and deoxyhypusine synthase. It was shown elsewhere that glutamyl– tRNA (gln) amidotransferase of other microorganisms can be inhibited by 6-diazo-5-oxonorleucine. Performing a half maximal inhibitory concentration (IC50) assay, we showed, that 6-diazo-5-oxonorleucine is also severely affecting viability of PF in blood plasma of the human host. We confirmed this by an in vivo study observing Plasmodium berghei infected mice

Avaliação econômica de sistemas conservacionistas no uso dos solos agrícolas: o caso do binômio trigo-soja no Rio Grande do Sul.

O uso intensivo de equipamento mecanizado nas atividades de lavoura determina um aumento no grau de compactação do solo na base da camada arável que, por sua vez, determina um aumento nas perdas de terra por erosão acompanhada de queda do potencial produtivo. Para contornar este problema - crescente na área devotada ao binómio trigo-soja no Rio Grande do Sul - recomendações têm sido elaboradas no sentido de adoção de sistemas de manejo do solo com mecanização reduzida e uso de subsolagem seguida de adubação verde. Para analisar a viabilidade econômica destas práticas conservacionistas desenvolveu-se um modelo dinâmico incorporando as variáveis relevantes do problema, procedendo-se à avaliação do efeito de decisões alternativas através de simulação em computador. Os resultados indicaram que os métodos mais conservacionistas no uso do solo no binômio trigo-soja apresentam considerável superioridade econômica sobre outras alternativas. Sugere-se, conseqüentemente, ação governamental capaz de acelerar a taxa de adoção dos sistemas de manejo mais ecológicos uma vez que estes carregam significativos benefícios privados e sociais

Title: Ex vivo coronary stent implantation evaluated with digital image correlation

Abstract: Intracoronary stenting (PCI) has become standard revascularization technique to reopen blocked arteries. Although significant progress in stenting technology and implantation techniques has been made a number of problems remain. Specifically, stent sizing and inflation pressures are still a matter of scientific debates. Despite a large number of biomechanical computational simulations experimental data are rare, likely due to technical difficulties to measure dilatation pressures and coronary dimensions in the same settings. Our study shows that valuable data can be obtained by employing digital image correlation for 3D strain measurement during stent inflation ex-vivo that can provide further insight into the stent-artery wall interactions. Keywords: Artery wall-stent interaction; coronary stent; digital image correlation; experimental implantation; strain. 3 Abstract/Introduction Intracoronary stenting (PCI) has become standard revascularization technique to reopen blocked arteries. Although significant progress in stenting technology and implantation techniques has been made a number of problems remain Despite a large number of biomechanical computational simulations [3, Methods Stent and PCI equipment The balloon-expandable CoCr coronary stent Kaname TM (Terumo Corporation, Tokyo, Japan) with nominal diameter 3.5 mm, and length 15 mm (at pressure 0.9 MPa; and diameter 3.73 mm at 1.6 MPa) was used in this study. The stent was premounted on PCI dilatation catheter RX-2 (Terumo Corporation). Sample The sample of the main branch of the left coronary artery was obtained from autopsy. The male donor was 40 years old and atherosclerotic lesions were presented inside the sample. The experiment was performed 70 hours post mortem. Experiment The sample was mounted into the experimental setup ( Displacement measurement was based on 3D digital image correlation (DIC) conducted with commercial system Dantec Q-450 (Dantec Dynamics, Ulm, Germany). 4 DIC is non-contact optical method based on the stereoscopic principle which is becoming more popular especially within the strain measurement of geometrically nonuniform objects. The algorithm identifies material points on the object surface and the correlation between consecutive images allows material point tracking. Detailed description can be found in the literature The artery was recorded with two digital cameras (NanoSens Mk III, Dantec Dynamics; 1MPx CCD chip; lens Sigma EX, 105 mm, 1:2.8 D Macro) during the balloon expansion (sampling rate 25 Hz). In fully expanded state, the object ROI approx. 18*3 mm*mm was projected onto 600*300 px*px (in each camera). RX2 manometer was recorded with another camera to obtain time course of change of the balloon distending pressure (pressure transducer connected with PC was not available at the time of experiment). The stent was deployed within manual pressurization up to 1.6 MPa which spanned approximately 42 seconds. Results DIC revealed significant overloading of the artery by the expanded stent. The results are depicted in Principal strains' distribution (Green-Lagrange strain is considered within this study) shows artery response within maximally expanded stent. Principal vectors are predominantly aligned with the circumferential and longitudinal direction which is supposed to be the consequence of the cylindrical stent expansion. Circumferential deformation attains 0.5 mm/mm at the peak value which is far beyond physiological situation. The circumferential strain concentration appears non-symmetrically with respect to the length of the sample which is supposed to be the result of irregular reference geometry (an asymmetrical partially occluded lumen of the artery). Six points (P1-6) were chosen to illustrate specific strain values resulting from different loading conditions and atherosclerotic specimen in our experiment. Discussion This is a preliminary report concerning a stent implantation in ex-vivo settings employing a human coronary artery harvested from autopsy. The results suggest that 3D DIC is promising tool suitable for the evaluation of ex-vivo stent implantation potentially useful for validation of computational models and clinical considerations. Presented results suggest that overexpansion of a stent during deployment may overstretch the target site potentially resulting in implantation injury associated with restenosis and/or intimal tears associated with dissections. To obtain exact intraluminal dimensions during stent deployment optical coherence tomography or intravascular ultrasound (IVUS) would be required, currently not available in our laboratory. Nevertheless we plan to combine IVUS with 3D DIC in future experiments

Uncovering cis Regulatory Codes Using Synthetic Promoter Shuffling

Revealing the spectrum of combinatorial regulation of transcription at individual promoters is essential for understanding the complex structure of biological networks. However, the computations represented by the integration of various molecular signals at complex promoters are difficult to decipher in the absence of simple cis regulatory codes. Here we synthetically shuffle the regulatory architecture — operator sequences binding activators and repressors — of a canonical bacterial promoter. The resulting library of complex promoters allows for rapid exploration of promoter encoded logic regulation. Among all possible logic functions, NOR and ANDN promoter encoded logics predominate. A simple transcriptional cis regulatory code determines both logics, establishing a straightforward map between promoter structure and logic phenotype. The regulatory code is determined solely by the type of transcriptional regulation combinations: two repressors generate a NOR: NOT (a OR b) whereas a repressor and an activator generate an ANDN: a AND NOT b. Three-input versions of both logics, having an additional repressor as an input, are also present in the library. The resulting complex promoters cover a wide dynamic range of transcriptional strengths. Synthetic promoter shuffling represents a fast and efficient method for exploring the spectrum of complex regulatory functions that can be encoded by complex promoters. From an engineering point of view, synthetic promoter shuffling enables the experimental testing of the functional properties of complex promoters that cannot necessarily be inferred ab initio from the known properties of the individual genetic components. Synthetic promoter shuffling may provide a useful experimental tool for studying naturally occurring promoter shuffling

Risks and benefits of sharing patient information on social media: a digital dilemma

Social media (SoMe) has witnessed remarkable growth and emerged as a dominant method of communication worldwide. Platforms such as Facebook, X (formerly Twitter), LinkedIn, Instagram, TikTok, and YouTube have become important tools of the digital native generation. In the field of medicine, particularly, cardiology, attitudes towards SoMe have shifted, and professionals increasingly utilize it to share scientific findings, network with experts, and enhance teaching and learning. Notably, SoMe is being leveraged for teaching purposes, including the sharing of challenging and intriguing cases. However, sharing patient data, including photos or images, online carries significant implications and risks, potentially compromising individual privacy both online and offline. Privacy and data protection are fundamental rights within European Union treaties, and the General Data Protection Regulation (GDPR) serves as the cornerstone of data protection legislation. The GDPR outlines crucial requirements, such as obtaining ‘consent’ and implementing ‘anonymization’, that must be met before sharing sensitive and patient-identifiable information. Additionally, it is vital to consider the patient’s perspective and prioritize ethical and social considerations when addressing challenges associated with sharing patient information on SoMe platforms. Given the absence of a peer-review process and clear guidelines, we present an initial approach, a code of conduct, and recommendations for the ethical use of SoMe. In conclusion, this comprehensive review underscores the importance of a balanced approach that ensures patient privacy and upholds ethical standards while harnessing the immense potential of SoMe to advance cardiology practice and facilitate knowledge dissemination

Cardiovascular magnetic resonance physics for clinicians: part I

There are many excellent specialised texts and articles that describe the physical principles of cardiovascular magnetic resonance (CMR) techniques. There are also many texts written with the clinician in mind that provide an understandable, more general introduction to the basic physical principles of magnetic resonance (MR) techniques and applications. There are however very few texts or articles that attempt to provide a basic MR physics introduction that is tailored for clinicians using CMR in their daily practice. This is the first of two reviews that are intended to cover the essential aspects of CMR physics in a way that is understandable and relevant to this group. It begins by explaining the basic physical principles of MR, including a description of the main components of an MR imaging system and the three types of magnetic field that they generate. The origin and method of production of the MR signal in biological systems are explained, focusing in particular on the two tissue magnetisation relaxation properties (T1 and T2) that give rise to signal differences from tissues, showing how they can be exploited to generate image contrast for tissue characterisation. The method most commonly used to localise and encode MR signal echoes to form a cross sectional image is described, introducing the concept of k-space and showing how the MR signal data stored within it relates to properties within the reconstructed image. Before describing the CMR acquisition methods in detail, the basic spin echo and gradient pulse sequences are introduced, identifying the key parameters that influence image contrast, including appearances in the presence of flowing blood, resolution and image acquisition time. The main derivatives of these two pulse sequences used for cardiac imaging are then described in more detail. Two of the key requirements for CMR are the need for data acquisition first to be to be synchronised with the subject's ECG and to be fast enough for the subject to be able to hold their breath. Methods of ECG synchronisation using both triggering and retrospective gating approaches, and accelerated data acquisition using turbo or fast spin echo and gradient echo pulse sequences are therefore outlined in some detail. It is shown how double inversion black blood preparation combined with turbo or fast spin echo pulse sequences acquisition is used to achieve high quality anatomical imaging. For functional cardiac imaging using cine gradient echo pulse sequences two derivatives of the gradient echo pulse sequence; spoiled gradient echo and balanced steady state free precession (bSSFP) are compared. In each case key relevant imaging parameters and vendor-specific terms are defined and explained