Evaluation of cadmium and mercury on cardiovascular and neurological systems: Effects on humans and fish

Chemicals are at the top of public health concerns and metals have received much attention in terms of toxicological studies. Cadmium (Cd) and mercury (Hg) are among the most toxic heavy metals and are widely distributed in the environment. They are considered important factors involved in several organ disturbances. Heart and brain tissues are not among the first exposure sites to Cd and Hg but they are directly affected and may manifest intoxication reactions leading to death. Many cases of human intoxication with Cd and Hg showed that these metals have potential cardiotoxic and neurotoxic effects. Human exposure to heavy metals is through fish consumption which is considered as an excellent source of human nutrients. In the current review, we will summarize the most known cases of human intoxication with Cd and Hg, highlight their toxic effects on fish, and investigate the common signal pathways of both Cd and Hg to affect heart and brain tissues. Also, we will present the most common biomarkers used in the assessment of cardiotoxicity and neurotoxicity using Zebrafish model.The open-access finding of the present work is provided by the Qatar National Library (QATAR)

Biomechanical Investigation of Disturbed Hemodynamics-Induced Tissue Degeneration in Abdominal Aortic Aneurysms Using Computational and Experimental Techniques.

Abdominal aortic aneurysm (AAA) is the dilatation of the aorta beyond 50% of the normal vessel diameter. It is reported that 4-8% of men and 0.5-1% of women above 50 years of age bear an AAA and it accounts for ~15,000 deaths per year in the United States alone. If left untreated, AAA might gradually expand until rupture; the most catastrophic complication of the aneurysmal disease that is accompanied by a striking overall mortality of 80%. The precise mechanisms leading to AAA rupture remains unclear. Therefore, characterization of disturbed hemodynamics within AAAs will help to understand the mechanobiological development of the condition which will contribute to novel therapies for the condition. Due to geometrical complexities, it is challenging to directly quantify disturbed flows for AAAs clinically. Two other approaches for this investigation are computational modeling and experimental flow measurement. In computational modeling, the problem is first defined mathematically, and the solution is approximated with numerical techniques to get characteristics of flow. In experimental flow measurement, once the setup providing physiological flow pattern in a phantom geometry is constructed, velocity measurement system such as particle image velocimetry (PIV) enables characterization of the flow. We witness increasing number of applications of these complimentary approaches for AAA investigations in recent years. In this paper, we outline the details of computational modeling procedures and experimental settings and summarize important findings from recent studies, which will help researchers for AAA investigations and rupture mechanics

Computational modeling of motile cilia generated cerebral flow dynamics in zebrafish embryo

Background: Motile cilia are hair-like microscopic structures which move the fluids along the epithelial surfaces. Cilia cover a wide range of regions in the nervous system, such as the nasal cavity, spinal cord central canal, and brain ventricles. Motile cilia-driven cerebrospinal fluid (CSF) flow in the brain ventricles has an important role in the brain development. Embryos lacking motile cilia develop neurological defects due to altered CSF flow. Aim: To investigate the effect of motile-cilia motion on the altered CSF flow, and to understand the role of CSF flow in the brain development and physiology. Methods: The dynamics of motile-cilia driven flow is analyzed employing computational fluid dynamics (CFD) modeling. A 2D model is generated using the time-lapse microscopic movies showing movements of a fluorescently labeled motile-cilia in a zebrafish embryo (48-hour post-fertilization). The effects on the generated flow are elucidated by investigating the cilia beating angle, multiple cilia formations, and the phase difference between different ciliary beats. Results: Ciliary beating generated a directional flow in the form of a circulating vortex. The angle of ciliary beating significantly affected the flow velocity. As the angle between the wall and cilia decreases, the flow becomes more efficient by achieving higher velocities. Multiple cilia formations increased the flow velocity but the significance of multiple cilia is not as critical as the beating angle. Interestingly, phase difference between the multiple cilia beats increased the directional flow velocity. Conclusion: Motile-cilia generated flow dynamics are investigated, and it is concluded that out-of-phase multiple ciliary beating is the optimum form of beating in order to generate a directional flo

Numerical Investigation of the Fetal Left Heart Hemodynamics During Gestational Stages

Flow-driven hemodynamic forces on the cardiac tissues have critical importance, and have a significant role in the proper development of the heart. These mechanobiological mechanisms govern the cellular responses for the growth and remodeling of the heart, where the altered hemodynamic environment is believed to be a major factor that is leading to congenital heart defects (CHDs). In order to investigate the mechanobiological development of the normal and diseased hearts, identification of the blood flow patterns and wall shear stresses (WSS) on these tissues are required for an accurate hemodynamic assessment. In this study, we focus on the left heart hemodynamics of the human fetuses throughout the gestational stages. Computational fetal left heart models are created for the healthy fetuses using the ultrasound images at various gestational weeks. Realistic inflow boundary conditions are implemented in the models using the Doppler ultrasound measurements for resolving the specific blood flow waveforms in the mitral valve. Obtained results indicate that WSS and vorticity levels in the fetal left heart decrease with the development of the fetus. The maximum WSS around the mitral valve is determined around 36 Pa at the gestational week of 16. This maximum WSS decreases to 11 Pa at the gestational week of 27, indicating nearly three-times reduction in the peak shear stress. These findings reveal the highly dynamic nature of the left heart hemodynamics throughout the development of the human fetus and shed light into the relevance of hemodynamic environment and development of CHDs.Qatar National Research Fun

Computational Modeling of Motile Cilia-Driven Cerebrospinal Flow in the Brain Ventricles of Zebrafish Embryo.

Motile cilia are hair-like microscopic structures which generate directional flow to provide fluid transport in various biological processes. Ciliary beating is one of the sources of cerebrospinal flow (CSF) in brain ventricles. In this study, we investigated how the tilt angle, quantity, and phase relationship of cilia affect CSF flow patterns in the brain ventricles of zebrafish embryos. For this purpose, two-dimensional computational fluid dynamics (CFD) simulations are performed to determine the flow fields generated by the motile cilia. The cilia are modeled as thin membranes with prescribed motions. The cilia motions were obtained from a two-day post-fertilization zebrafish embryo previously imaged via light sheet fluorescence microscopy. We observed that the cilium angle significantly alters the generated flow velocity and mass flow rates. As the cilium angle gets closer to the wall, higher flow velocities are observed. Phase difference between two adjacent beating cilia also affects the flow field as the cilia with no phase difference produce significantly lower mass flow rates. In conclusion, our simulations revealed that the most efficient method for cilia-driven fluid transport relies on the alignment of multiple cilia beating with a phase difference, which is also observed in vivo in the developing zebrafish brain.Part of this work was supported by a FRIPRO grant from the Research Council of Norway (N.J.-Y. grant number 314189). The publication of this article was funded by the Qatar National Library

Hemodynamic and Structural Comparison of Human Fetal Heart Development Between Normally Growing and Hypoplastic Left Heart Syndrome-Diagnosed Hearts

Congenital heart defects (CHDs) affect a wide range of societies with an incidence rate of 1.0–1.2%. These defects initiate at the early developmental stage and result in critical health disorders. Although genetic factors play a role in the formation of CHDs, the occurrence of cases in families with no history of CHDs suggests that mechanobiological forces may also play a role in the initiation and progression of CHDs. Hypoplastic left heart syndrome (HLHS) is a critical CHD, which is responsible for 25–40% of all prenatal cardiac deaths. The comparison of healthy and HLHS hearts helps in understanding the main hemodynamic differences related to HLHS. Echocardiography is the most common imaging modality utilized for fetal cardiac assessment. In this study, we utilized echocardiographic images to compare healthy and HLHS human fetal hearts for determining the differences in terms of heart chamber dimensions, valvular flow rates, and hemodynamics. The cross-sectional areas of chamber dimensions are determined from 2D b-mode ultrasound images. Valvular flow rates are measured via Doppler echocardiography, and hemodynamic quantifications are performed with the use of computational fluid dynamics (CFD) simulations. The obtained results indicate that cross-sectional areas of the left and right sides of the heart are similar for healthy fetuses during gestational development. The left side of HLHS heart is underdeveloped, and as a result, the hemodynamic parameters such as flow velocity, pressure, and wall shear stress (WSS) are significantly altered compared to those of healthy hearts.This study was funded by the Qatar National Research Fund (QNRF), National Priority Research Program (NPRP 10-0123-170222). Open access funding was provided by the Qatar National Library

Blood Flow Disturbance and Morphological Alterations Following the Right Atrial Ligation in the Chick Embryo.

Collectively known as congenital heart defects (CHDs), cardiac abnormalities at birth are the most common forms of neonatal defects. Being principally responsible for the heart's pumping power, ventricles are particularly affected by developmental abnormalities, such as flow disturbances or genomic defects. Hypoplastic Right Heart Syndrome (HRHS) is a rare disease where the right ventricle is underdeveloped. In this study, we introduce a surgical procedure performed on chick embryo, termed right atrial ligation (RAL) for disturbing hemodynamics within the right heart aiming in order to generate an animal model of HRHS. RAL is a new surgical manipulation, similar to the well-studied left atrial ligation (LAL) surgery but it induces the hemodynamic change into the right side of the heart. After inducing RAL, We utilized techniques such as Doppler ultrasound, x-ray micro-CT, histology, and computational fluid dynamics (CFD) analysis, for a comprehensive functional and structural analysis of a developing heart. Our results displayed that RAL does not induce severe flow disturbance and ventricular abnormalities consistent with clinical findings. This study allows us to better understand the hemodynamics-driven CHD development and sensitivities of ventricles under disturbed flows

A Novel Deep Learning Technique for Morphology Preserved Fetal ECG Extraction from Mother ECG using 1D-CycleGAN

Monitoring the electrical pulse of fetal heart through a non-invasive fetal electrocardiogram (fECG) can easily detect abnormalities in the developing heart to significantly reduce the infant mortality rate and post-natal complications. Due to the overlapping of maternal and fetal R-peaks, the low amplitude of the fECG, systematic and ambient noises, typical signal extraction methods, such as adaptive filters, independent component analysis, empirical mode decomposition, etc., are unable to produce satisfactory fECG. While some techniques can produce accurate QRS waves, they often ignore other important aspects of the ECG. Our approach, which is based on 1D CycleGAN, can reconstruct the fECG signal from the mECG signal while maintaining the morphology due to extensive preprocessing and appropriate framework. The performance of our solution was evaluated by combining two available datasets from Physionet, "Abdominal and Direct Fetal ECG Database" and "Fetal electrocardiograms, direct and abdominal with reference heartbeat annotations", where it achieved an average PCC and Spectral-Correlation score of 88.4% and 89.4%, respectively. It detects the fQRS of the signal with accuracy, precision, recall and F1 score of 92.6%, 97.6%, 94.8% and 96.4%, respectively. It can also accurately produce the estimation of fetal heart rate and R-R interval with an error of 0.25% and 0.27%, respectively. The main contribution of our work is that, unlike similar studies, it can retain the morphology of the ECG signal with high fidelity. The accuracy of our solution for fetal heart rate and R-R interval length is comparable to existing state-of-the-art techniques. This makes it a highly effective tool for early diagnosis of fetal heart diseases and regular health checkups of the fetus.Comment: 24 pages, 11 figure

Microfluidic-based virus detection methods for respiratory diseases

With the recent SARS-CoV-2 outbreak, the importance of rapid and direct detection of respiratory disease viruses has been well recognized. The detection of these viruses with novel technologies is vital in timely prevention and treatment strategies for epidemics and pandemics. Respiratory viruses can be detected from saliva, swab samples, nasal fluid, and blood, and collected samples can be analyzed by various techniques. Conventional methods for virus detection are based on techniques relying on cell culture, antigen-antibody interactions, and nucleic acids. However, these methods require trained personnel as well as expensive equipment. Microfluidic technologies, on the other hand, are one of the most accurate and specific methods to directly detect respiratory tract viruses. During viral infections, the production of detectable amounts of relevant antibodies takes a few days to weeks, hampering the aim of prevention. Alternatively, nucleic acid–based methods can directly detect the virus-specific RNA or DNA region, even before the immune response. There are numerous methods to detect respiratory viruses, but direct detection techniques have higher specificity and sensitivity than other techniques. This review aims to summarize the methods and technologies developed for microfluidic-based direct detection of viruses that cause respiratory infection using different detection techniques. Microfluidics enables the use of minimal sample volumes and thereby leading to a time, cost, and labor effective operation. Microfluidic-based detection technologies provide affordable, portable, rapid, and sensitive analysis of intact virus or virus genetic material, which is very important in pandemic and epidemic events to control outbreaks with an effective diagnosis.Qatar National Research Fun