1,567 research outputs found
Optimization and biological validation of an in vitro assay using the transfected Dm28c/pLacZ Trypanosoma cruzi strain
There is an urgent need to develop safer and more effective drugs for Chagas disease, as the current treatment relies on benznidazole (BZ) and nifurtimox (NFX). Using the Trypanosoma cruzi Dm28c strain genetically engineered to express the Escherichia coli β-galactosidase gene, lacZ, we have adapted and validated an easy, quick and reliable in vitro assay suitable for high-throughput screening for candidate compounds with anti-T. cruzi activity. In vitro studies were conducted to determine trypomastigotes sensitivity to BZ and NFX from Dm28c/pLacZ strain by comparing the conventional labour-intensive microscopy counting method with the colourimetric assay. Drug concentrations producing the lysis of 50% of trypomastigotes (lytic concentration 50%) were 41.36 and 17.99 μM for BZ and NFX, respectively, when measured by microscopy and 44.74 and 38.94 μM, for the colourimetric method, respectively. The optimal conditions for the amastigote development inhibitory assay were established considering the parasite-host relationship (i.e. multiplicity of infection) and interaction time, the time for colourimetric readout and the incubation time with the β-galactosidase substrate. The drug concentrations resulting in 50% amastigote development inhibition obtained with the colourimetric assay were 2.31 μM for BZ and 0.97 μM for NFX, similar to the reported values for the Dm28c wild strain (2.80 and 1.5 μM, respectively). In summary, a colourimetric assay using the Dm28c/pLacZ strain of T. cruzi has been set up, obtaining biologically meaningful sensibility values with the reference compounds on both trypomastigotes and amastigotes forms. This development could be applied to high-throughput screening programmes aiming to identify compounds with anti-T. cruzi in vitro activity
Diseño de matriz de riesgos laborales para establecer los niveles de peligros a los que están expuestos los trabajadores de la Distribuidora Lácteos El Establo en Simijaca Cundinamarca para el segundo semestre 2022
El presente trabajo de investigación se realizó en la empresa Lácteos el Establo ubicada en el municipio de Simijaca Cundinamarca, donde participaron los empleados de todas las áreas, las variables de este estudio es la identificación de peligros en los puestos de trabajo mediante la elaboración de una matriz de riesgos.
Así mismo, identificar los peligros especialmente para la parte operativa de la Distribuidora Lácteos el establo, para evitar posibles accidentes laborales que pongan en peligro a los trabajadores. La identificación es de gran importancia para evaluar los protocolos de manejo en caso de accidente,
Partiendo que actualmente la empresa en estudio no se ha realizado la identificación de estos peligros está enfocado a los nuevos proyectos que tiene la organización, que son capacitaciones sobre los seguridad y salud en el trabajo Para ello se realizara una encuesta en donde se identificarán las necesidades para mitigar los riesgos a los que ellos están expuestos y cómo influyen estas dentro de la organización para asimismo plantear una metodología para promover el desarrollo de la organización, entre otros cambios.This research work was conducted in the factory Lácteos el Establo located in Simijaca Cundinamarca town, where employees from all areas participated, the variables of this study is the identification of hazards in the workplace through the development of a risk matrix.
Likewise, identify the hazards especially for the operational part of the Distribuidora Lácteos el Establo, to avoid possible occupational accidents that endanger workers. The identification is of great importance to evaluate the management protocols in case of an accident,
Since currently the company under study has not made the identification of these hazards is focused on the new projects that the organization has, which are training on safety and health at work. For this, a survey will be conducted to identify the needs to mitigate the risks to which they are exposed and how they influence these within the organization to also propose a methodology to promote the development of the organization, among other changes
Deep attention super-resolution of brain magnetic resonance images acquired under clinical protocols
Vast quantities of Magnetic Resonance Images (MRI) are routinely acquired in clinical practice but, to speed up acquisition, these scans are typically of a quality that is sufficient for clinical diagnosis but sub-optimal for large-scale precision medicine, computational diagnostics, and large-scale neuroimaging collaborative research. Here, we present a critic-guided framework to upsample low-resolution (often 2D) MRI full scans to help overcome these limitations. We incorporate feature-importance and self-attention methods into our model to improve the interpretability of this study. We evaluate our framework on paired low- and high-resolution brain MRI structural full scans (i.e., T1-, T2-weighted, and FLAIR sequences are simultaneously input) obtained in clinical and research settings from scanners manufactured by Siemens, Phillips, and GE. We show that the upsampled MRIs are qualitatively faithful to the ground-truth high-quality scans (PSNR = 35.39; MAE = 3.78E−3; NMSE = 4.32E−10; SSIM = 0.9852; mean normal-appearing gray/white matter ratio intensity differences ranging from 0.0363 to 0.0784 for FLAIR, from 0.0010 to 0.0138 for T1-weighted and from 0.0156 to 0.074 for T2-weighted sequences). The automatic raw segmentation of tissues and lesions using the super-resolved images has fewer false positives and higher accuracy than those obtained from interpolated images in protocols represented with more than three sets in the training sample, making our approach a strong candidate for practical application in clinical and collaborative research
Blood-brain barrier leakage hotspots collocating with brain lesions due to sporadic and monogenic small vessel disease
Relationship Between Venules and Perivascular Spaces in Sporadic Small Vessel Diseases
Background and Purpose—
Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging.
Methods—
We developed a visual venular quantification method to examine the spatial relationship between venules and PVS. We recruited patients with lacunar stroke or minor nondisabling ischemic stroke and performed brain magnetic resonance imaging and retinal imaging. We quantified venules on gradient echo or susceptibility-weighted imaging and PVS on T2-weighted magnetic resonance imaging in the centrum semiovale and then determined overlap between venules and PVS. We assessed associations between venular count and patient demographic characteristics, vascular risk factors, small vessel disease features, retinal vessels, and venous sinus pulsatility.
Results—
Among 67 patients (69% men, 69.0±9.8 years), only 4.6% (range, 0%–18%) of venules overlapped with PVS. Total venular count increased with total centrum semiovale PVS count in 55 patients after accounting for venule-PVS overlap (β=0.468 [95% CI, 0.187–0.750]) and transverse sinus pulsatility (β=0.547 [95% CI, 0.309–0.786]) and adjusting for age, sex, and systolic blood pressure.
Conclusions—
Despite increases in both visible PVS and suspected venules, we found minimal spatial overlap between them in patients with sporadic small vessel disease, suggesting that most magnetic resonance imaging-visible centrum semiovale PVS are periarteriolar rather than perivenular
Do baseline characteristics affect depressive symptoms treatment success? Posthoc subgroup analysis from the CONEMO trials
Objective: As a secondary trial plan analysis, we aim to examine whether participant characteristics, measured before randomization, modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO – Emotional Control) on recovery from depression that has presented a substantive impact on previous research.Method: Mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest, including suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension). We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models.Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of the scores of depressive symptoms in at least 50% at three-month follow-up) were observed amongst older and wealthier participants in Lima (p-values 0.030 and 0.001, respectively). At the same time, there was no evidence of such differential effects in São Paulo or any other secondary outcomes level in both countries.Conclusions: Digital intervention used in primary care settings needs to be accessible. We conclude that the technological intervention CONEMO has no heterogeneity effects on most subgroups studied, except income and age in the Lima trial
Imaging NeuroVascular, Endothelial and STructural Integrity in prepAration to TrEat Small Vessel Diseases. The INVESTIGATE-SVDs study Protocol
Background: Sporadic cerebral small vessel disease (SVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) share clinical and neuroimaging features and possibly vascular dysfunction(s). However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre. The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres. Methods: We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) and CADASIL in Edinburgh, Maastricht and Munich. We will perform detailed clinical and neuropsychological phenotyping of the participants, and neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous and CSF flow and pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) and multishell diffusion imaging. Participants will measure their blood pressure (BP) and its variability over seven days using a telemetric device. Discussion: INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility and CSF flow in sporadic SVD and CADASIL using a multisite, multimodal MRI protocol. We aim to establish associations between these measures of vascular function, risk factors particularly BP and its variability, and brain parenchymal lesions in these two SVD phenotypes. Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures and sample size estimates for future trials
Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project
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