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Biomedical subjects

Min Rao

Publications and source records attributed to Min Rao.

8 recordsLinked to original sources

Causal Relationships Between Oral Microbiota and Inflammatory Skin Diseases.

INTRODUCTION AND AIMS: The oral microbiome has been increasingly linked to systemic inflammation and immune dysregulation, but whether specific oral bacteria causally contribute to inflammatory skin diseases remains unclear due to confounding and reverse causation. This study aimed to assess the causal effects of 43 oral microbiota taxa on the risk of five inflammatory skin diseases using a Mendelian randomization (MR) approach. METHODS: We performed a two-sample MR analysis using genetic instruments for oral microbiota derived from publicly available genome-wide association studies and outcome data from the FinnGen consortium. Causal effects of oral taxa on systemic lupus erythematosus, vitiligo, pemphigus, localized scleroderma, and dermatitis herpetiformis were estimated. The inverse-variance weighted method served as the primary analysis, complemented by sensitivity analyses to evaluate horizontal pleiotropy, heterogeneity, and reverse causality. RESULTS: MR analyses identified several putative causal associations between oral microbiota and inflammatory skin diseases. Genus Granulicatella and an unknown Streptococcus species (ASV0009) showed causal effects on systemic lupus erythematosus. Family Lachnospiraceae_[XIV] and an unknown Rothia species (ASV0016) were associated with vitiligo. Five oral microbiota taxa demonstrated causal associations with pemphigus. Actinomyces species micronuciformis was linked to localized scleroderma. Order Fusobacteriales and an unknown Neisseria species (ASV0004) were associated with dermatitis herpetiformis. No significant heterogeneity or horizontal pleiotropy was detected in sensitivity analyses. CONCLUSION: This MR study provides genetic evidence supporting a causal role of specific oral bacteria in the development of several inflammatory skin diseases, highlighting the oral microbiome as a potential contributor to cutaneous autoimmunity and inflammation. CLINICAL RELEVANCE: Our findings highlight the putative role of the oral microbiome as a plausible candidate for mechanistic and clinical investigations into the prevention or adjunctive management of selected inflammatory skin diseases. However, oral hygiene improvement, targeted antimicrobials, and other microbiota-directed interventions were not directly tested in this MR study and remain hypothetical strategies requiring validation in experimental and clinical studies.

Humans↗

The Ultrasonix 500RP: a commercial ultrasound research interface.

Unlike researchers in magnetic resonance imaging who have considerable access to high level tools and to data at a very basic level on their scanners, those involved with ultrasound have found little in the way of meaningful and widespread access to even the most basic echo signals in their clinical systems. Interest has emerged, however, in ultrasound research interfaces on commercial scanners to provide access to raw ultrasound data and control of basic research functions. This paper describes initial experience gained on one such ultrasound system. The Ultrasonix 500RP system provides research access to the data at multiple points in the signal processing chain and allows control over most imaging parameters. The Ultrasonix system allows for three methods of research control. One is implemented along with the standard clinical imaging software using "mouseover" screens on the periphery of the application window. These screens are configured by the user to display various signal processing variables, which can be modified in real time. Second, the system can be controlled via a user-written remote control client application interacting through the clinical exam software. Lastly, the user can write a complete application which initializes the basic ultrasound module but need not use the Ultrasonix clinical exam software. All of the modes can be done locally on the scanner itself or via a network, and are based on software developed in C++ with libraries supplied with the scanner. Two examples are presented in this paper from the evaluation of the system in "real world" applications. Measurements of absolute backscatter coefficients and attenuation coefficients versus frequency are shown and elastograms utilizing spatial compounding are described.

Biomedical Research↗

Spatial-angular compounding for elastography using beam steering on linear array transducers.

Spatial-angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Under this method, compounded elastograms are obtained from a spatially weighted average of local strain estimated from radio frequency (rf) echo signals acquired at different insonification angles. In previous work, the acquisition of the rf signals was performed through the lateral translation of a phased-array transducer. Clinical applications of angular compounding would, however, require the utilization of beam steering on linear-array transducers to obtain angular data sets, which is more efficient than translating phased-array transducers. In this article, we investigate the performance of angular compounding for elastography by using beam steering on a linear-array transducer. Quantitative experimental results demonstrate that spatial angular compounding provides significant improvement in both the elastographic signal-to-noise ratio and the contrast-to-noise ratio. For the linear array transducer used in this study, the optimum angular increment is around 1.5 degrees-3.75 degrees, and the maximum angle that can be used in angular compounding should not exceed 10 degrees.

Artifacts↗

Correlation analysis of the beam angle dependence for elastography.

Signal decorrelation is a major source of error in the displacements estimated using correlation techniques for elastographic imaging. Previous papers have addressed the variation in the correlation coefficient as a function of the applied compression for a finite window size and an insonification angle of zero degrees. The recent use of angular beam-steered radio-frequency echo signals for spatial angular compounding and shear strain estimation have demonstrated the need for understanding signal decorrelation artifacts for data acquired at different beam angles. In this paper, we provide both numerical and closed form theoretical solutions of the correlation between pre- and post-compression radio-frequency echo signals acquired at a specified beam angle. The expression for the correlation coefficient obtained is a function of the beam angle and the applied compression for a finite duration window. Accuracy of the theoretical results is verified using tissue-mimicking phantom experiments on a uniformly elastic phantom using beam-steered data acquisitions on a linear array transducer. The theory predicts a faster decorrelation with changes in the beam or insonification angle for longer radio-frequency echo signal segments and at deeper locations in the medium. Theoretical results provide useful information for improving angular compounding and shear strain estimation techniques for elastography.

Elasticity↗

Mutants of Mycobacterium smegmatis unable to grow at acidic pH in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone.

Mycobacterium smegmatis is able to grow and survive at acidic pH, and exhibits intracellular pH homeostasis under these conditions. In this study, the authors have identified low proton permeability of the cytoplasmic membrane, and high cytoplasmic buffering capacity, as determinants of intrinsic acid resistance of M. smegmatis. To identify genes encoding proteins involved in protecting cells from acid stress, a screening method was developed using the electrogenic protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP). CCCP was used to suppress intrinsic acid resistance of M. smegmatis. The screen involved exposing cells to pH 5.0 in the presence of CCCP, and survivors were rescued at various time intervals on solid medium at pH 7.5. Cells capable of responding to intracellular acidification (due to CCCP-induced proton equilibration) will survive longer under these conditions than acid-sensitive cells. From a total pool of 5000 transposon (Tn611) insertion mutants screened, eight acid-sensitive M. smegmatis mutants were isolated. These acid-sensitive mutants were unable to grow at pH 5.0 in the presence of 1-5 microM CCCP, a concentration not lethal to the wild-type strain mc2155. The DNA flanking the site of Tn611 was identified using marker rescue in Escherichia coli, and DNA sequencing to identify the disrupted locus. Acid-sensitive mutants of M. smegmatis were disrupted in genes involved in phosphonate/phosphite assimilation, methionine biosynthesis, the PPE multigene family, xenobiotic-response regulation and lipid biosynthesis. Several of the acid-sensitive mutants were also defective in stationary-phase survival, suggesting that overlapping stress protection systems exist in M. smegmatis.

Bacterial Proteins↗

Spatial angular compounding for elastography without the incompressibility assumption.

Spatial-angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Previous results using spatial angular compounding, however, were based on the use of the tissue incompressibility assumption. Compounded elastograms were obtained from a spatially-weighted average of local strain estimated from radiofrequency echo signals acquired at different insonification angles. In this paper, we present a new method for reducing the noise artifacts in the axial strain elastogram utilizing a least-squares approach on the angular displacement estimates that does not use the incompressibility assumption. This method produces axial strain elastograms with higher image quality, compared to noncompounded axial strain elastograms, and is referred to as the least-squares angular-compounding approach for elastography. To distinguish between these two angular compounding methods, the spatial-angular compounding with angular weighting based on the tissue incompressibility assumption is referred to as weighted compounding. In this paper, we compare the performance of the two angular-compounding techniques for elastography using beam steering on a linear-array transducer. Quantitative experimental results demonstrate that least-squares compounding provides comparable but smaller improvements in both the elastographic signal-to-noise ratio and the contrast-to-noise ratio, as compared to the weighted-compounding method. Ultrasound simulation results suggest that the least-squares compounding method performs better and provide accurate and robust results when compared to the weighted compounding method, in the case where the incompressibility assumption does not hold.

Algorithms↗

Intracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG.

Mycobacteria are likely to encounter acidic pH in the environments they inhabit; however intracellular pH homeostasis has not been investigated in these bacteria. In this study, Mycobacterium smegmatis and Mycobacterium bovis [Bacille Calmette--Guérin (BCG)] were used as examples of fast- and slow-growing mycobacteria, respectively, to study biochemical and physiological responses to acidic pH. M. smegmatis and M. bovis BCG were able to grow at pH values of 4.5 and 5.0, respectively, suggesting the ability to regulate internal pH. Both species of mycobacteria maintained their internal pH between pH 6.1 and 7.2 when exposed to decreasing external pH and the maximum Delta pH observed was approximately 2.1 to 2.3 units for both bacteria. The Delta pH of M. smegmatis at external pH 5.0 was dissipated by protonophores (e.g. carbonyl cyanide m-chlorophenylhydrazone), ionophores (e.g. monensin and nigericin) and N,N'-dicyclohexylcarbodiimide (DCCD), an inhibitor of the proton-translocating F(1)F(0)-ATPase. These results demonstrate that permeability of the cytoplasmic membrane to protons and proton extrusion by the F(1)F(0)-ATPase plays a key role in maintaining internal pH near neutral. Correlations between measured internal pH and cell viability indicated that the lethal internal pH for both strains of mycobacteria was less than pH 6.0. Compounds that decreased internal pH caused a rapid decrease in cell survival at acidic pH, but not at neutral pH. These data indicate that both strains of mycobacteria exhibit intracellular pH homeostasis and this was crucial for the survival of these bacteria at acidic pH values.

Cell Membrane Permeability↗