PNPLA3 Genotype and Dietary Fat Modify Concentrations of Plasma and Fecal Short Chain Fatty Acids and Plasma Branched-Chain Amino Acids.

The GG genotype of the Patatin-like phosphatase domain-containing 3 (PNPLA3), dietary fat, short-chain fatty acids (SCFA) and branched-chain amino acids (BCAA) are linked with non-alcoholic fatty liver disease. We studied the impact of the quality of dietary fat on plasma (p) and fecal (f) SCFA and p-BCAA in men homozygous for the PNPLA3 rs738409 variant (I148M). Eighty-eight randomly assigned men (age 67.8 ± 4.3 years, body mass index 27.1 ± 2.5 kg/m2) participated in a 12-week diet intervention. The recommended diet (RD) group followed the National and Nordic nutrition recommendations for fat intake. The average diet (AD) group followed the average fat intake in Finland. The intervention resulted in a decrease in total p-SCFAs and iso-butyric acid in the RD group (p = 0.041 and p = 0.002). Valeric acid (p-VA) increased in participants with the GG genotype regardless of the diet (RD, 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.005 and AD, 3.8 ± 0.3 to 9.7 ± 8.5 µmol/g, p = 0.015). Also, genotype relation to p-VA was seen statistically significantly in the RD group (CC: 3.7 ± 0.4 to 4.2 ± 1.7 µmol/g and GG: 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.0026 for time and p = 0.004 for time and genotype). P-VA, unlike any other SCFA, correlated positively with plasma gamma-glutamyl transferase (r = 0.240, p = 0.025). Total p-BCAAs concentration changed in the AD group comparing PNPLA3 CC and GG genotypes (CC: 612 ± 184 to 532 ± 149 µmol/g and GG: 587 ± 182 to 590 ± 130 µmol/g, p = 0.015 for time). Valine decreased in the RD group (p = 0.009), and leucine decreased in the AD group (p = 0.043). RD decreased total fecal SCFA, acetic acid (f-AA), and butyric acid (f-BA) in those with CC genotype (p = 0.006, 0.013 and 0.005, respectively). Our results suggest that the PNPLA3 genotype modifies the effect of dietary fat modification for p-VA, total f-SCFA, f-AA and f-BA, and total p-BCAA.

Greater increases in intratumoral apparent diffusion coefficients after chemoradiotherapy predict better overall survival of patients with cervical cancer.

PURPOSE: To evaluate whether 1) the intratumoral apparent diffusion coefficients (ADCs) change during cervical cancer treatment and 2) the pretreatment ADC values or their change after treatment predict the treatment outcome or overall survival of patients with cervical cancer. METHODS: We retrospectively enrolled 52 patients with inoperable cervical cancer treated with chemoradiotherapy, who had undergone diffusion weighted MRI before treatment and post external beam radiotherapy (EBRT) and concurrent chemotherapy. A subgroup of patients (n = 28) underwent altogether six consecutive diffusion weighted MRIs; 1) pretreatment, 2) post-EBRT and concurrent chemotherapy; 3-5) during image-guided brachytherapy (IGBT) and 6) after completing the whole treatment course. To assess interobserver and intertechnique reproducibility two observers independently measured the ADCs by drawing freehand a large region of interest (L-ROI) covering the whole tumor and three small ROIs (S-ROIs) in areas with most restricted diffusion. RESULTS: Reproducibility was equally good for L-ROIs and S-ROIs. The pretreatment ADCs were higher in L-ROIs (883 mm2/s) than in S-ROIs (687 mm2/s, P < 0.001). The ADCs increased significantly between the pretreatment and post-EBRT scans (L-ROI: P < 0.001; S-ROI: P = 0.001). The ADCs remained significantly higher than pretreatment values during the whole IGBT. Using S-ROIs, greater increases in ADCs between pretreatment and post-EBRT MRI predicted better overall survival (P = 0.018). CONCLUSION: ADC values significantly increase during cervical cancer treatment. Greater increases in ADC values between pretreatment and post-EBRT predicted better overall survival using S-ROIs. Standardized methods for timing and delineation of ADC measurements are advocated in future studies.

Contrast-enhanced ultrasound: a new tool for imaging the superficial lymphatic vessels of the upper limb.

BACKGROUND: Despite the new lymphatic imaging methods, there is still a need for a straightforward method of detecting lymphatic abnormalities. Our goal was to investigate the feasibility of applying a contrast enhanced ultrasound (CEUS) procedure as a new approach for visualising the superficial lymphatic vessels of the upper limb. METHODS: Thirty healthy volunteers were examined with CEUS after bilateral intradermal injection of Sonazoid® contrast agent in distal antebrachium. We registered factors affecting intradermal injections, imaging of the superficial lymphatic vessels and the enhancement time of contrast agent reaching the levels of elbow and axilla. RESULTS: CEUS imaging of superficial lymphatic vessels was successful in 59 of 60 upper limbs (98.3%). Median [interquartile ranges] enhancement times of contrast agent to reach the elbow (right 18 s [11-25], left 15 s [12-25]) and axilla (right 77 s [33-118], left 66 s [42-115]) were equally fast. Successful intradermal injections were found to result in two types of contrast enhancement (strong or moderate), while the enhancement time depended on the type of the successful injection. No major differences in enhancement times were observed related to sex, body mass index, age, or side of the arm. CONCLUSIONS: The superficial lymphatic pathways of the upper limb can be visualised with CEUS imaging. Since enhancement time is dependent on the success of intradermal injections, one must pay attention to the injection technique. Further studies are needed to evaluate the method in patients with lymphatic function disorders such as breast cancer therapy related lymphoedema.

2D-shear wave elastography in the evaluation of suspicious superficial inguinal lymph nodes: Reproducibility and region of interest selection.

PURPOSE: To assess the ability of 2D-Shear wave elastography (2D-SWE) to evaluate its reproducibility, to define the optimal orientation and size of the region of interest (ROI), and to differentiate benign from malignant inguinal lymph nodes (LNs). METHOD: Thirty-two suspicious inguinal LNs from 21 patients were evaluated with 2D-SWE. SWE measurements were obtained in two orthogonal planes. To investigate reproducibility, sensitivity and specificity, circular ROIs with a diameter of 1 mm, 2 mm, 3 mm and 5 mm were placed on the cortex of the LNs. Additionally, one freehand ROI was drawn covering majority of the LN. Two observers performed five sets of SWE measurements for each ROI size. All LNs underwent core needle biopsy or were surgically removed. RESULTS: The 3 mm ROI for Mean-E in axial plane showed high interrater agreement [intraclass correlation coefficient (ICC) 0.899] with the cut-off value of 7.31 kPa resulting in 88.9% sensitivity and 60.9% specificity for differentiating malignant from benign LNs. In benign LNs, mean elasticity of the ROI was lower (7.68 ± 3.82 kPa; range, 3.41-15.40 kPa) compared to the malignant LNs (15.81 ± 10.61 kPa; range, 3.86-36.45 kPa). CONCLUSIONS: The most reproducible way to measure stiffness in inguinal LNs is a 3 mm circular ROI centered on the cortex of the LN in axial plane. Elasticity values were higher in the malignant LNs reflecting the stiffer nature of the metastatic LNs. 2D-SWE offers a noninvasive ultrasonographic tool to assess superficial inguinal lymph nodes with high reproducibility.

In vivo assessment of the passive stretching response of the bicompartmental human semitendinosus muscle using shear-wave elastography.

The semitendinosus muscle contains distinct proximal and distal compartments arranged anatomically in series but separated by a tendinous inscription, with each compartment innervated by separate nerve branches. Although extensively investigated in other mammals, compartment-specific mechanical properties within the human semitendinosus have scarcely been assessed in vivo. Experimental data obtained during muscle-tendon unit stretching (e.g., slack angle) can also be used to validate and/or improve musculoskeletal model estimates of semitendinosus muscle force. The purpose of this study was to investigate the passive stretching response of proximal and distal human semitendinosus compartments to distal (knee) joint extension. Using two-dimensional shear-wave elastography, we bilaterally obtained shear moduli of both semitendinosus compartments from 14 prone-positioned individuals at 10 knee flexion angles [from 90° to 0° (full extension) at 10° intervals]. Passive muscle mechanical characteristics (slack angle, slack shear modulus, and the slope of the increase in shear modulus) were determined for each semitendinosus compartment by fitting a piecewise exponential model to the shear modulus-joint angle data. We found no differences between compartments or legs for slack angle, slack shear modulus, or the slope of the increase in shear modulus. We also found that the experimentally determined slack angle occurred at ∼15°-80° higher knee flexion angles compared with estimates from two commonly used musculoskeletal models, depending on participant and model used. Overall, these findings demonstrate that passive shear modulus-joint angle curves do not differ between proximal and distal human semitendinosus compartments and provide experimental data to improve semitendinosus force estimates derived from musculoskeletal models.NEW & NOTEWORTHY We conducted an elastography-based investigation of the passive stretching response of the proximal and distal compartments of the human semitendinosus muscle and found no difference in shear modulus-joint angle curves between compartments. We also found that common musculoskeletal models tend to misestimate semitendinosus slack angle, most likely due to typical model assumptions. These results provide an important step toward a better understanding of semitendinosus passive muscle mechanics and improving computational estimates of muscle force.