Background
Influenza A virus (IAV) causes a wide range of extrarespiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined.
Methods
Here, we sought to use transcriptional profiling, virology, histology, and echocardiograms to investigate the role of a high-fat diet in IAV-associated cardiac damage.
Results
Transcriptional profiling showed that, compared to their low-fat counterparts (LF mice), mice fed a high-fat diet (HF mice) had impairments in inflammatory signaling in the lung and heart after IAV infection. This was associated with increased viral titers in the heart, increased left ventricular mass, and thickening of the left ventricular wall in IAV-infected HF mice compared to both IAV-infected LF mice and uninfected HF mice. Retrospective analysis of clinical data revealed that cardiac complications were more common in patients with excess weight, an association which was significant in 2 out of 4 studies.
Conclusions
Together, these data provide the first evidence that a high-fat diet may be a risk factor for the development of IAV-associated cardiovascular damage and emphasizes the need for further clinical research in this area.
Mammographic density (MD) is a strong independent risk factor for breast cancer. Traditional screening for MD using X-ray mammography involves ionising radiation, which is not suitable for young women, those with previous radiation exposure, or those having undergone a partial mastectomy. Therefore, alternative approaches for MD screening that do not involve ionising radiation will be important as the clinical use of MD increases, and as more frequent MD testing becomes desirable for research purposes. We have previously demonstrated the potential utility of spin relaxation-based, single-sided portable-NMR measurements for the purpose of MD quantification. We present here a more refined analysis by quantifying breast tissue density in excised samples on a continuous scale (0% to 100% fibroglandular tissue content) using micro-CT (CT), and comparing the results to spin-relaxation and diffusion portable-NMR measurements of the same samples. CT analysis of mammary tissues containing high-and low-MD (HMD and LMD, respectively) regions had Hounsfield Unit (HU) histograms with a bimodal pattern, with HMD regions exhibiting significantly higher HU values than LMD regions. Quantitative MD (%HMD) values obtained using CT exhibited an excellent correlation with portable-NMR results, namely longitudinal spin-relaxation time constants (T1) and the relative tissue water content obtained from portable-NMR diffusion measurements (R 2 =0.92, p<0.0001 and R 2 =0.96, p<0.0001, respectively). These findings are consistent with our previous results demonstrating relatively high water content in HMD breast tissue, consistent with the high proportion of fibroglandular tissue, FGT, which in turn contains more abundant water-carrying HSPG proteins. We observed an excellent correlation between the T1 values and diffusion NMR-measured relative tissue water content (R 2 =0.94, p<0.0001). These findings demonstrate, for the first time, the ability of single-sided portable NMR to accurately quantify MD in vitro on a continuous scale. The results also indicate that portable-NMR analysis can assist in the identification of features underpinning MD, namely FGT and adipose tissue content. Future work will involve application of portable NMR to quantifying MD in vivo.
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