SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome with inclusion of pathobionts.

The microbiota of the nasopharyngeal tract (NT) play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. This study characterizes the effects of SARS-CoV-2 infection on human nasopharyngeal microbiomes and their relevant metabolic functions. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 patients = 8, recovered humans = 7, and healthy people = 7) were collected, and underwent to RNAseq-based metagenomic investigation. Our RNAseq data mapped to 2281 bacterial species (including 1477, 919 and 676 in healthy, COVID-19 and recovered metagenomes, respectively) indicating a distinct microbiome dysbiosis. The COVID-19 and recovered samples included 67% and 77% opportunistic bacterial species, respectively compared to healthy controls. Notably, 79% commensal bacterial species found in healthy controls were not detected in COVID-19 and recovered people. Similar dysbiosis was also found in viral and archaeal fraction of the nasopharyngeal microbiomes. We also detected several altered metabolic pathways and functional genes in the progression and pathophysiology of COVID-19. The nasopharyngeal microbiome dysbiosis and their genomic features determined by our RNAseq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.

Early Detection of Acute Kidney Injury by Neutrophil Gelatinase Associated Lipocalin in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules after injury, potentially allowing early identification of acute kidney injury (AKI) after cardiac surgery. However, the diagnostic performance of NGAL has varied widely in clinical studies and it remains unknown what factors modify the relationship between NGAL and AKI. The main objective of the study was to determine the efficacy of NGAL in early detection of AKI among the CABG patients undergoing cardiopulmonary bypass (CPB). This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh in collaboration with the Department of Biochemistry, BSMMU among 42 patients admitted into the Department of Cardiac Surgery, Ibrahim Cardiac Hospital and Research Institute, Dhaka Bangladesh from July 2014 to June 2015. For the measurement of NGAL, urine samples were obtained before surgery and 6 hours after commencement of CPB. Serum creatinine was measured preoperatively and 6, 24 and 48 hours postoperatively. Increase in the serum creatinine level at 6, 24 and 48 hours after surgery was used to analyze the diagnostic value of urinary NGAL. In this study 42 CABG patients with no known renal insufficiency planned to have CPB were included. Receiver-operator characteristic (ROC) was constructed by using NGAL, which gave a cut off value of ≥185.90ng/ml. Eight patients were AKI positive among them 6(75.0%) patients were NGAL positive and 2(25.0%) were NGAL negative. Diagnosis of AKI was delayed by 24-48 hours by serum creatinine measurement. This study has demonstrated that level of urinary NGAL concentration at 6 hours post CPB increased before the increase of serum creatinine level and NGAL is an early predictor of AKI in adult cardiac surgical patients. The early detection of renal injury by NGAL may allow earlier intervention in patients with high risk for AKI.

Association Between Smoking and COVID-19 Severity: Evidence from Bangladesh.

PURPOSE: Previous studies have explored several risk factors for coronavirus disease 2019 (COVID-19) severity, but there is still a lack of association with smoking. Our study aims to find out the association between smoking and COVID-19 severity. SUBJECTS AND METHODS: This comparative study was conducted among hospitalized severely and critically ill COVID-19 patients, as well as asymptomatic, mild, and moderate patients from the list of the city corporation (Dhaka, Bangladesh), as confirmed by reverse-transcription polymerase chain reaction (RT-PCR). A total of 2022 adults aged ≥18 years were enrolled in this study. RESULTS: The mean age of the patients was 41.17 years; 66.96% of the patients were male, 57.02% were aged above 35 years, and 81.50% of the patients had ever been married; and 33.09% cases were mild and 14.99% were severe. Among the patients, 29.4% were ever-smokers. Smoking status, duration, and frequency, and the presence of comorbidities were significantly associated with COVID-19 severity (p<0.001). Ever-smokers were 1.35 times (95% CI: 0.74-2.45), 1.30 times (95% CI: 0.58-2.87), and 2.45 times (95% CI: 1.07-5.61) more likely to be mild, severe, and critical cases in comparison to non-smokers. CONCLUSION: This study revealed a strong association between smoking and COVID-19 severity that calls for mass awareness and cessation campaigns from governments and voluntary organizations.

DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53.

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.

Theoretical derivation of SNR, CNR and spatial resolution for a local adaptive strain estimator for elastography.

Conventional techniques in elastography estimate the axial strain as the gradient of the displacement (time-delay) estimates obtained using cross-correlation of pre- and temporally stretched postcompression radiofrequency (RF) A-line segments. The use of a constant stretch factor for stretching the postcompression A-line is not adequate in the presence of heterogeneous targets that are commonly encountered. This led to the development of several adaptive strain estimation techniques in elastography. Yet, a theoretical framework for the image quality of adaptive strain estimation has not been established. In this work, we develop theoretical expressions for the image quality [measured in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution] of elastograms obtained using an adaptive strain estimator developed by Alam et al. (1998). We show a linear trade-off between the SNR and axial resolution of the strain elastogram with respect to the window length used for strain estimation. The CNR shows a quadratic tradeoff with the axial resolution with respect to the window length. The SNR, CNR and axial resolution are shown to improve with the ultrasonic bandwidth.

Elastographic imaging using staggered strain estimates.

Conventional techniques in elastography estimate strain as the gradient of the displacement estimates obtained through crosscorrelation of pre- and postcompression rf A-lines. In these techniques, the displacements are estimated over overlapping windows and the strains are estimated as the gradient of the displacement estimates over adjacent windows. The large amount ofnoise at high window overlaps may result in poor quality elastograms, thus restricting the applicability of conventional strain estimation techniques to low window overlaps, which, in turn, results in a small number of pixels in the image. To overcome this restriction, we propose a multistep strain estimation technique. It computes the first elastogram using nonoverlapped windows. In the next step, the data windows are shifted by a small distance (small fraction of window size) and another elastogram is produced. This is repeated until the cumulative shift equals/exceeds the window size and all the elastograms are staggered to produce the final elastogram. Simulations and experiments were performed using this technique to demonstrate significant improvement in the elastographic signal-to-noise ratio (SNRe) and the contrast-to-noise ratio (CNRe) at high window overlaps over conventional strain estimation techniques, without noticeable loss of spatial resolution. This technique might be suitable for reducing the algorithmic noise in the elastograms at high window overlaps.

Organochlorine pesticides and heavy metals in muscle and ovaries of Gulf coast striped bass (Morone saxatilis) from the Apalachicola River, Florida, USA.

Eight female Gulf coast striped bass (Morone saxatilis) broodfish collected for induced spawning from the Apalachicola River below the Jim Woodruff Lock and Dam were analyzed for organochlorine pesticides (OCs) and metals in muscle and ovarian tissues. Chemical analyses revealed that muscle and ovaries contained detectable amounts of OCs and metals. Concentrations of p,p'-DDE, a derivative of the pesticide DDT, in muscle and ovary (0.54 and 0.65 microg/g, respectively) were significantly higher than alpha-chlordane, dieldrin, and p,p'-DDD. The presence of p,p'-DDE, an antiandrogenic compound, in females suggests that the compound also may be present in male striped bass. Concentrations of Cr, Hg, Mg, and Mn were higher in muscle than in ovarian tissues. Concentrations of Hg have almost doubled in muscle tissues (0.85 microg/g) and tripled in ovaries (0. 15 microg/g) in our samples, compared with the data from 1986 to 1989. Organochlorine pesticides and metal contaminants were present in muscle and ovarian tissues of adult females and may have been retarding development of eggs leading to low hatching rates.

Organochlorine, PCB, PAH, and metal concentrations in eggs of loggerhead sea turtles (Caretta caretta) from northwest Florida, USA.

Composite samples of unhatched and physically unaltered loggerhead sea turtle, Caretta caretta, eggs collected from 20 nests along northwest Florida were analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and metals. Chemical analyses revealed that turtle eggs contained detectable amounts of metals, PAHs, and PCBs. Only one OCP, p,p'-DDD, was detected, and its presence was restricted to eggs from two nesting sites. None of the PCB concentrations exceeded the Food and Drug Administration's (FDA) action limit. Concentrations of dioxin-like PCB congeners, 105, 118, and 126, and total PCBs were also detected and are contributors to the toxic burden of loggerhead sea turtle eggs. Concentrations of PAHs, 1,2,5,6-dibenzanthracene, 1-methyl naphthalene, C1-naphthalene and naphthalene were variable at nesting sites. Comparison of mean metal burdens in eggs from different beaches suggested that no uniform geographic gradients exist. Presence of OCPs, PCBs, PAHs and metals and their additive or synergistic toxicity is a concern to loggerhead sea turtle eggs; however, additive or synergistic impacts for loggerhead sea turtles are largely undocumented.

Serological response to immunization with tetanus toxoid.

A total of two hundred women were immunized with tetanus toxoid vaccine. Two batches of toxoid prepared at the Institute of Public Health (IPH), Dhaka and one batch of imported vaccines, were being used by the EPI in Bangladesh for immunization. Each hundred women were immunized by IPH and imported vaccine. Two human doses were given in one month interval. Blood samples from all the study subjects were collected on the day of 1st dose and one month after second dose. Both the preimmunized sera and the sera after vaccination were tested to determine the antibody titre against tetanus toxoid by the haemagglutination method. The preimmunized sera showed the presence of protective antibody in 50(25%) subjects who had the history of previous immunization. Including these initial antitoxin positive cases the seroconversions found among 95% and 96% of the study population respectively after immunization with IPH and imported toxoids, which were 93.05% and 94.87% when these 50 subjects were excluded. No significant difference (p = 1.0) was observed between the immunity of the subjects after receiving IPH and imported vaccine. Antibody titre of initial tetanus-antitoxin positive cases raised eight folds after getting more doses. The result gave fair indication of the antigenicity of all the toxoids used in the study.

Direct strain estimation in elastography using spectral cross-correlation.

Spectral estimation of tissue strain has been performed previously by using the centroid shift of the power spectrum or by estimating the variation in the mean scatterer spacing in the spectral domain. The centroid shift method illustrates the robustness of the direct, incoherent strain estimator. In this paper, we present a strain estimator that uses spectral cross-correlation of the pre- and postcompression power spectrum. The centroid shift estimator estimates strain from the mean center frequency shift, while the spectral cross-correlation estimates the shift over the entire spectrum. Spectral cross-correlation is shown to be more sensitive to small shifts in the power spectrum and, thus, provides better estimation for smaller strains when compared to the spectral centroid shift. Spectral cross-correlation shares all the advantages gained using the spectral centroid shift, in addition to providing accurate and precise strain estimation for small strains. The variance and noise properties of the spectral strain estimators quantified by their respective strain filters are also presented.

The effect of nonlinear signal transformations on bias errors in elastography.

We have reported several artifacts in elastography (1991). These include mechanical artifacts, such as stress concentration, and signal processing artifacts, such as zebras, which are caused by bias errors incurred during the estimation of the peak of correlation functions using a curve-fitting method. We investigate the bias errors and show that bias errors in curve-fitting methods are substantially increased because of nonlinear operations on the echo signals that reduce other errors. We also show that, for typical sampling rates, the bias errors can be ignored in the absence of these nonlinear operations.

Elastographic axial resolution criteria: an experimental study.

In elastography, window size has been typically used synonymously with resolution. Strain is estimated by computing the gradient of the displacement estimates, which have a direct dependence on the window size. However, the resolution is also dependent on the separation between these windows. The intricate relationship between the window size, window shift, and resolution has not previously been explored. In this article, we perform a controlled simulation experiment to evaluate the relationship among elastographic axial resolution, window size, and window shift. We conclude that the axial resolution can be expressed as a bilinear function of window size and window shift, the latter having a much larger weight.

Power spectral strain estimators in elastography.

Elastography can produce quality strain images in vitro and in vivo. Standard elastography uses a coherent cross-correlation technique to estimate tissue displacement and tissue strain using a subsequent gradient operator. Although coherent estimation methods generally have the advantage of being highly accurate and precise, even relatively small undesired motions are likely to cause enough signal decorrelation to produce significant degradation of the elastogram. For elastography to become more universally practical in such applications as hand-held, intravascular and abdominal imaging, the limitations associated with coherent strain estimation methods that require tissue and system stability, must be overcome. In this paper, we propose the use of a spectral-shift method that uses a centroid shift estimate to measure local strain directly. Furthermore, we also show theoretically that a spectral bandwidth method can also provide a direct strain estimation. We demonstrate that strain estimation using the spectral-shift technique is moderately less precise, but far more robust than the cross-correlation method. A theoretical analysis, simulations and experimental results are used to illustrate the properties associated with this method.

Elastography: ultrasonic estimation and imaging of the elastic properties of tissues.

The basic principles of using sonographic techniques for imaging the elastic properties of tissues are described, with particular emphasis on elastography. After some preliminaries that describe some basic tissue stiffness measurements and some contrast transfer limitations of strain images are presented, four types of elastograms are described, which include axial strain, lateral strain, modulus and Poisson's ratio elastograms. The strain filter formalism and its utility in understanding the noise performance of the elastographic process is then given, as well as its use for various image improvements. After discussing some main classes of elastographic artefacts, the paper concludes with recent results of tissue elastography in vitro and in vivo.

An adaptive strain estimator for elastography.

Elastography is based on the estimation of strain due to applied tissue compression. In conventional elastography, strain is computed from the gradient of the displacement estimates between gated pre- and postcompression echo signals. Gradient-based estimation methods are known to be susceptible to noise. In elastography, in addition to the electronic noise, a principal source of estimation error is the decorrelation of the echo signal as a result of tissue compression (decorrelation noise). Temporal stretching of postcompression signals previously was shown to reduce the decorrelation noise. In this paper, we introduce a novel estimator that uses the stretch factor itself as an estimator of the strain. It uses an iterative algorithm that adaptively maximises the correlation between the pre- and postcompression echo signals by appropriately stretching the latter. We investigate the performance of this adaptive strain estimator using simulated and experimental data. The estimator has exhibited a vastly superior performance compared with the conventional gradient-based estimator.

A deconvolution filter for improvement of time-delay estimation in elastography.

In elastography, tissue under investigation is compressed, and the resulting strain is estimated from the gradient of displacement estimates. Therefore, it is important to accurately estimate the displacements (time-delay) for good quality elastograms. A principal source of error in time-delay estimation in elastography is the decorrelation of the echo signal due to tissue compression (decorrelation noise). Temporal stretching of the postcompression signals has been shown to reduce the decorrelation noise at small strains. In this article, we present a deconvolution filter that reduces the decorrelation even further when applied in conjunction with signal stretching. The performance of the proposed filter is evaluated using simulated data.

The combined effect of signal decorrelation and random noise on the variance of time delay estimation.

Tissue motion and elasticity imaging techniques commonly use time delay estimation (TDE) for the assessment of tissue displacement. The performance of these techniques is limited because the signals are corrupted by various factors including electronic noise, quantization, and speckle decorrelation. Speckle decorrelation is caused by changes in the coherent interference among scatterers when the tissue moves relative to the ultrasound beam. In time delay estimation, the effect of noise is usually addressed through the signal-to-noise ratio (SNR) term. Decorrelation, often a significant source of error in medical ultrasound, is commonly described in terms of the correlation coefficient. A relationship between the correlation coefficient and the SNR was previously derived in the literature, for identical signals corrupted by uncorrelated random noise. In this paper, we derive the relationship between the peak of the correlation coefficient function and the SNR for two jointly stationary signals when a delay is present between the signals. Recently, an expression for the Cramer-Rao lower bound (CRLB) has been derived in the literature for partially decorrelated signals in terms of the SNR and the correlation coefficient. Since the applicability of the CRLB is determined not only by the SNR, but also by the correlation coefficient, it is important to unify the expression for the CRLB for partially correlated signals. In this paper, we derive an expression for the CRLB in term of an equivalent SNR converted from the correlation coefficient using an SNR-p relationship, and show this expression to be equivalent to the expression for CRLB. We also corroborate the validity of the SNR-p expression with a simulation. Using this formulation, correlation measurements can be converted to SNR to obtain a composite SNR. The use of this composite SNR in lieu of those in the CRLB expression in the literature allows the extension of the literature results to the solution of the common TDE problems that involve signal decorrelation.

Reduction of signal decorrelation from mechanical compression of tissues by temporal stretching: applications to elastography.

Elastography is based on the estimation of strain due to tissue compression. Strain is computed from the estimates of time delays between gated precompression and postcompression echo signals. Time delay estimates are obtained from the location of the peak of the crosscorrelation function between gated precompression and postcompression signals. It is of paramount importance to accurately estimate the time delays for good quality elastograms. A main source of time delay estimation (TDE) error in elasticity imaging is the decorrelation of the echo signal as a result of tissue compression (decorrelation noise). The effect of decorrelation on the mean of the crosscorrelation function and the correlation coefficient has been investigated. The expected value of the cross-correlation function between the precompression and postcompression signals was shown to be a filtered version of the autocorrelation function of the precompression signal. In this article, the effect of temporal stretching of the postcompression echo signal on the cross-correlation function will be investigated along the same line. The applied compression is assumed to be uniform; the decorrelations introduced by the lateral and elevational tissue movements are ignored. The theory predicts that if the postcompression echo signals are stretched before the TDE step, then for small strains, the cross-correlation function very closely resembles the autocorrelation function. For larger strains, correlation is improved if temporal stretching is applied. The theory is corroborated by results from simulation and homogeneous phantom experiments. Thus, the decorrelation noise in elastograms can be reduced by temporal stretching of the postcompression signal.

On the use of envelope and RF signal decorrelation as tissue strain estimators.

Bamber and Bush (1995) used the correlation coefficient for freehand elasticity imaging. Varghese and Ophir (1996) found it to be a biased estimator of strain with a large variability. In this study, we systematically investigate the effect of changes in various system and processing parameters on the performance of the correlation coefficient strain estimator, and demonstrate, using simulated data, that noise and frequency-dependent attenuation can introduce variable bias in this estimator.