Enhanced stiffness in peri-cancerous tissue: a marker of poor prognosis in papillary thyroid carcinoma with lymph node metastasis.

BACKGROUND: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients. METHOD: A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data. RESULTS: The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ±â€…5.63 vs 66.05 ±â€…4.46; Eshell/E: 1.20 ±â€…1.72 vs 1.09 ±â€…1.10, P < .001). When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively). The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E- group (all P < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group. CONCLUSIONS: Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM.

Diagnostic performance of a new two-dimensional shear wave elastography expression using siemens ultrasound system combined with ACR TI-RADS for classification of benign and malignant thyroid nodules: A prospective multi-center study.

Objective: The present study aimed to evaluate the efficacy of a new two-dimensional shear wave elastography (2D-SWE) method using a Siemens ultrasound system and its combination with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for the differential diagnosis of benign and malignant thyroid nodules. Methods: Conventional ultrasound images and 2D-SWE (E-whole-mean and E-stiffest-mean) were prospectively analyzed in 593 thyroid nodules from 543 patients. Nodules were divided into diameter (D) ≤10 mm and D > 10 mm groups and graded using ACR TI-RADS. The receiver operating characteristic curve was plotted using pathological findings as the gold standard. Diagnostic performance was compared among 2D-SWE, ACR TI-RADS, and their combination. Results: The area under the curve (AUC) for E-whole-mean was higher than that for E-stiffest-mean (0.858 vs. 0.790, P < 0.001), which indicated that it was the better 2D-SWE parameter for differentiating malignant nodules from benign nodules with an optimal cut-off point of 11.36 kPa. In the all-sizes group, the AUC for E-whole-mean was higher than that for ACR TI-RADS (0.858 vs. 0.808, P < 0.001). The combination of E-whole-mean and ACR TI-RADS resulted in a higher AUC (0.929 vs. 0.858 vs. 0.808, P < 0.001), sensitivity (87.0% vs. 80.3% vs. 85.2%), specificity (85.1% vs. 74.0% vs. 73.6%), accuracy (86.3% vs. 78.1% vs. 81.1%), positive predictive value (91.5% vs. 85.1% vs. 85.6%), and negative predictive value (78.0% vs. 67.0% vs. 72.9%) compared to E-whole-mean or ACR TI-RADS alone. The AUC for the combination of 2D-SWE and ACR TI-RADS was superior to that for E-whole-mean or ACR TI-RADS alone in both D ≤ 10 mm and D > 10 mm groups (P < 0.001). Conclusion: As the better 2D-SWE parameter, E-whole-mean had a higher diagnostic power than ACR TI-RADS and enhanced the diagnostic performance of ACR TI-RADS when identifying benign and malignant thyroid nodules. The combination of E-whole-mean and ACR TI-RADS improved the diagnostic performance compared to using ACR TI-RADS alone, providing a new and reliable method for the clinical diagnosis of thyroid nodules.

Multibeam minimum variance beamforming for ring array ultrasound imaging.

Objective. Delay-and-sum (DAS) and minimum variance (MV) are two of the most important beamformers researched in ultrasound imaging. Compared with DAS, MV beamformer is different in respect of the aperture weights calculation, and can enhance the image quality by minimizing interference signal power. Various MV beamformers in linear array are studied, but linear array only provides a limited field of view. Ring array can provide better resolution and a full viewing angle; however, few studies have been explored based on ring array transducers.Approach. In this study, we proposed the multibeam MV (MB-MV) beamformer based on the conventional MV to enhance the image quality in ring array ultrasound imaging. To assess the effectiveness of the proposed approach, we conducted simulations, phantom experiments, andin vivohuman experiments to compare MB-MV with DAS and spatial smoothing (SS) MV beamformers.Main results. The results show that the MB-MV method achieves at least 50% enhancement in terms of full width at half maximum compared to the others. Additionally, the MB-MV method improves the contrast ratio by approximate 6 dB and 4 dB compared with DAS and SS MV, respectively.Significance. This work demonstrates the feasibility of MB-MV method for ring array ultrasound imaging, and proves that MB-MV can improve the imaging quality in medical ultrasound imaging. According to our results, MB-MV method provides great potential in distinguishing between lesion and non-lesion areas in clinics, and further promotes the practical application of ring arrays in ultrasound imaging.

Convolutional neural network based on automatic segmentation of peritumoral shear-wave elastography images for predicting breast cancer.

Objective: Our aim was to develop dual-modal CNN models based on combining conventional ultrasound (US) images and shear-wave elastography (SWE) of peritumoral region to improve prediction of breast cancer. Method: We retrospectively collected US images and SWE data of 1271 ACR- BIRADS 4 breast lesions from 1116 female patients (mean age ± standard deviation, 45.40 ± 9.65 years). The lesions were divided into three subgroups based on the maximum diameter (MD): ≤15 mm; >15 mm and ≤25 mm; >25 mm. We recorded lesion stiffness (SWV1) and 5-point average stiffness of the peritumoral tissue (SWV5). The CNN models were built based on the segmentation of different widths of peritumoral tissue (0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm) and internal SWE image of the lesions. All single-parameter CNN models, dual-modal CNN models, and quantitative SWE parameters in the training cohort (971 lesions) and the validation cohort (300 lesions) were assessed by receiver operating characteristic (ROC) curve. Results: The US + 1.0 mm SWE model achieved the highest area under the ROC curve (AUC) in the subgroup of lesions with MD ≤15 mm in both the training (0.94) and the validation cohorts (0.91). In the subgroups with MD between15 and 25 mm and above 25 mm, the US + 2.0 mm SWE model achieved the highest AUCs in both the training cohort (0.96 and 0.95, respectively) and the validation cohort (0.93 and 0.91, respectively). Conclusion: The dual-modal CNN models based on the combination of US and peritumoral region SWE images allow accurate prediction of breast cancer.

Convolutional Neural Network for Predicting Thyroid Cancer Based on Ultrasound Elastography Image of Perinodular Region.

We aimed to develop deep learning models based on perinodular regions' shear-wave elastography (SWE) images and ultrasound (US) images of thyroid nodules (TNs) and determine their performances in predicting thyroid cancer. A total of 1747 American College of Radiology Thyroid Imaging Reporting & Data System 4 (TR4) thyroid nodules (TNs) in 1582 patients were included in this retrospective study. US images, SWE images, and 2 quantitative SWE parameters (maximum elasticity of TNs; 5-point average maximum elasticity of TNs) were obtained. Based on US and SWE images of TNs and perinodular tissue, respectively, 7 single-image convolutional neural networks (CNN) models [US, internal SWE, 0.5 mm SWE, 1.0 mm SWE, 1.5 mm SWE, 2.0 mm SWE of perinodular tissue, and whole SWE region of interest (ROI) image] and another 6 fusional-image CNN models (US + internal SWE, US + 0.5 mm SWE, US + 1.0 mm SWE, US + 1.5 mm SWE, US + 2.0 mm SWE, US + ROI SWE) were established using RestNet18. All of the CNN models and quantitative SWE parameters were built on a training cohort (1247 TNs) and evaluated on a validation cohort (500 TNs). In predicting thyroid cancer, US + 2.0 mm SWE image CNN model obtained the highest area under the curve in 10 mm < TNs ≤ 20 mm (0.95 for training; 0.92 for validation) and TNs > 20 mm (0.95 for training; 0.92 for validation), while US + 1.0 mm SWE image CNN model obtained the highest area under the curve in TNs ≤ 10 mm (0.95 for training; 0.92 for validation). The CNN models based on the fusion of SWE segmentation images and US images improve the radiological diagnostic accuracy of thyroid cancer.

Fluorinated Copolypeptide-Stabilized Microbubbles with Maleimide-Decorated Surfaces as Long-Term Ultrasound Contrast Agents.

Gas-filled microbubbles (MBs) have been clinically used as ultrasound (US) contrast agents for disease diagnosis and treatment. However, it remains a great challenge to resolve the dilemma of stability and contrast enhancement of MBs. Herein, amphiphilic copolypeptides bearing fluorinated blocks are synthesized to stabilize perfluorocarbon (PFC)-filled MBs, exhibiting unique stability under both long-term storage and US imaging conditions. The fluorinated inner layer reduces the internal Laplace pressure and greatly improves the stability of MBs, which can be further reinforced by crosslinking of the dipropargyl-containing middle blocks. To overcome the suppressed nonlinear oscillation of polymer shells, maleimide groups are introduced onto the surface of MBs, enabling in situ reaction with plasma proteins to enhance second harmonic signals without compromising the stability of MBs, conferring better US imaging performance than that of SonoVueTM MBs.

Evaluation of Tissue Stiffness Around Lesions by Sound Touch Shear Wave Elastography in Breast Malignancy Diagnosis.

The aim of the study described here was to assess the evaluation of tissue stiffness around lesions by sound touch shear wave elastography (STE) in breast malignancy diagnosis. This was an institutional ethics committee-approved, single-center study. A total of 90 women with breast masses examined with conventional ultrasound and STE were eligible for enrollment from December 2020 to July 2021. The maximum and mean elastic values of masses, Emax and Emean, were determined. Shell function was used to measure the maximum and mean elastic values of tissues around masses in annular shells 0.5, 1.0, 1.5 and 2.0 mm wide, recorded as corresponding Emax-shell and Emean-shell. All parameters were analyzed and compared with histopathologic results. Receiver operating characteristic curves were constructed to assess diagnostic performance. Logistic regression analysis was conducted to determine the best diagnostic model. Collagen fiber content of tissues around breast lesions was evaluated using Masson staining and ImageJ software. Ninety women with breast masses were included in this study; 50 had benign (mean diameter 15.84 ± 4.39 mm) and 40 had malignant (mean diameter 17.40 ± 5.42 mm) masses. The diagnostic value of Emax-shell-2.0 was the highest (area under the curve = 0.930) with a sensitivity of 87.5% and specificity of 88%. According to stepwise logistic regression analysis, Emax-shell-2.0 and age were independent predictors of malignancy. Emax-shell-2.0 was also found to be highly correlated with the collagen fiber content of tissue in the malignant group (r = 0.877). Tissue stiffness around lesions measured by STE is a useful metric in identifying malignant breast masses by reflecting collagen fiber content, and Emax-shell-2.0 performs best.

Analysis of Risk Factors Associated With Central Lymph Node Metastasis in Papillary Thyroid Carcinoma With cT1N0 Stage.

Aim: Annual T1 stage papillary thyroid carcinoma (PTC) incidence rates continue to rise, yet the optimal treatment for this cancer type remains controversial. Central lymph node metastasis (CLNM) is a critical determinant in the context of treatment decision-making. While several prior studies have evaluated patients with clinica l T1a(cT1a) stage PTC, there have been fewer analyses of clinical T1b(cT1b) disease to date. The present study was thus formulated to explore predictors of CLNM in patients with cT1a and cT1b stage PTC. Methods: A retrospective analysis of data including clinicopathological characteristics and BRAFV600E mutation status was conducted for 452 PTC patients undergoing surgical treatment. Logistic univariate and multivariate analyses were performed to identify risk factors associated with CLNM in particular patients' characteristics and the accuracy of the established logistic regression models was evaluated using the R software platform. Results: Respective CLNM incidence rates in cT1a and cT1b disease were 39.39% and 67.21%. Factors associated with a higher risk of CLNM among PTC(cT1a) patients included male sex, young age, tumor size, contact with capsule, and multifocality as determined through comparisons of the area under the curve for logistic regression models. Whereas male sex and age were associated with CLNM risk in PTC(cT1b) patients in univariate and multivariate analyses, age was the only risk factor associated with CLNM incidence among women with PTC(cT1b). Conclusion: Predictors of CLNM differ between PTC patients with cT1a and cT1b stage disease, and a comprehensive assessment of these risk factors should thus be conducted when designing individualized treatment regimens for PTC patients.

Evaluation of Ultrasound Elastography Combined With Chi-Square Automatic Interactive Detector in Reducing Unnecessary Fine-Needle Aspiration on TIRADS 4 Thyroid Nodules.

BACKGROUND: Conventional ultrasound diagnosis of thyroid nodules (TNs) had a high false-positive rate, resulting in many unnecessary fine-needle aspirations (FNAs). OBJECTIVE: This study aimed to establish a simple algorithm to reduce unnecessary FNA on TIRADS 4 TNs using different quantitative parameters of ultrasonic elasticity and chi-square automatic interactive detector (CHAID) method. METHODS: From January 2020 to May 2021, 432 TNs were included in the study, which were confirmed by FNA or surgical pathology. Each TN was examined using conventional ultrasound, sound touch elastography, and Shell measurement function. The quantitative parameters E and E shell were recorded, and the E shell/E values were calculated for each TN. The diagnostic performance of the quantitative parameters was evaluated using the receiver operating characteristic curves. The CHAID was used to classify and analyze the quantitative parameters, and the prediction model was established. RESULTS: A total of 226 TNs were malignant and 206 were benign. E shell and E shell/E ratio were included in the classification algorithm, which showed a depth of two ramifications (E shell/E ≤ 0.988 or 0.988-1.043 or >1.043; if E shell/E ≤ 0.988, then E shell ≤ 64.0 or 64.0-74.0 or >74.0; if E shell/E = 0.988-1.043, then E shell ≤ 66.0 or > 66.0; if E shell/E >1.043, then E shell ≤ 69.0 or >69.0). The unnecessary FNAs could have been avoided in 57.3% of the cases using this algorithm. CONCLUSION: The prediction model using quantitative parameters had high diagnostic performance; it could quickly distinguish benign lesions and avoid subjective influence to some extent.

Ectopic Schistosomiasis Involving Axillary Lymph Nodes.

Axillary lymph node schistosomiasis is a form of ectopic schistosomiasis, in which the Schistosoma adult worms or eggs are infected in the axillary lymph nodes. A 53-year-old woman visited our hospital with a small mass in the right armpit, which had been present for over 1 month. Histological examination of biopsy samples from the right axillary lymph nodes revealed granulomas containing calcified Schistosoma eggs. This is the first authentic case of ectopic schistosomiasis identified in the axillary lymph nodes.

Clinical and ultrasound features correlated with a heavy axillary nodal tumor burden in colon cancer.

Aim: This study aimed to investigate the correlation between the pathologic and ultrasound (US) characteristics of colon cancer and the heavy axillary nodal burden. Methods: In total, 631 patients diagnosed with invasive colon cancer were recruited with ethical ratification. Results: The unitary pathologic features correlated with heavy axillary lymph nodal burden included the age of patient (p = 0.035), tumor size (p = 0.001), lymph node metastasis (p = 0.001), lymphovascular invasion (p = 0.020) and pathology type (p = 0.012). The independent US characteristics correlated with heavy axillary nodal burden included posterior acoustic enhancement (p = 0.006). Heavy axillary nodal burden was correlated with tumor size, lymph node metastasis, lymphovascular invasion and pathology type. Conclusion: Tumor size, lymph node metastasis and posterior acoustic can be used to predict the axillary lymph node tumor burden.

Assessment of perinodular stiffness in differentiating malignant from benign thyroid nodules.

OBJECTIVE: We evaluated the diagnostic accuracy of perinodular stiffness, four risk stratification systems (RSSs) (KWAK-TIRADS, ACR-TIRADS, EU-TIRADS, and C-TIRADS), and the combination of perinodular stiffness and the four RSSs in differentiating malignant from benign thyroid nodules (TNs). METHODS: A total of 788 TNs in 726 patients were examined with conventional ultrasound (US) examination and sound touch elastography (STE). All TNs were classified by each of the four RSSs. The stiffness inside (E) the TNs was measured by STE. The stiffness of the 2.0-mm perinodular region (Eshell) was measured with the Shell measurement function of STE. The diagnostic performances of four RSSs, the E values, and the Eshell values were evaluated. All TNs were further divided into subgroups based on size (≤ 10 mm group and > 10 mm group). RESULTS: Ninety-six TNs were classified as benign and 692 as malignant. Among the single-method approaches, ACR-TIRADS showed the highest AUC (0.77) for differentiating malignant from benign TNs for all TNs included. Eshell showed the highest AUC (0.75) in differentiating malignant from benign TNs for TNs with sizes ≤ 10 mm, and there were no significant differences in AUC among all single methods for diagnosis of TNs with sizes > 10 mm (P > 0.05). The combination of C-TIRADS and Eshell/E yielded the highest AUC for all TNs (0.83) and for TNs with size ≤ 10 mm (0.85) compared with other combinations. CONCLUSIONS: Eshell/E combined with conventional US improves the diagnostic accuracy in TNs and may reduce unnecessary fine-needle aspiration.

Value of ultrasound elastography combined with contrast-enhanced ultrasound and micro-flow imaging in differential diagnosis of benign and malignant breast lesions.

OBJECTIVE: Breast cancer is one of the most common malignant tumors in women and shows a rising incidence at younger ages. Therefore, early diagnosis is of great significance for treatment and prognosis. This study aimed to compare the value of ultrasound elastography (UE) combined with contrast-enhanced ultrasound (CEUS) and micro-flow imaging (MFI) in differential diagnosis of benign and malignant lesions of the breast. METHODS: The sonographic characteristics of UE and CEUS as well as the vascular characteristics of MFI of 109 breast lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) category 4, confirmed by surgical or biopsy pathology were retrospectively analyzed. Receiver operating characteristic (ROC) curves were used to compare the diagnostic efficacy of the three examination modalities, either alone or in combination. RESULTS: Of the 109 breast lesions, 78 lesions were pathologically diagnosed as malignant and 31 as benign. At diagnosis, the area under the ROC curve (AUC), sensitivity, specificity, and accuracy of UE were 0.8495, 65.38%, 83.87% and 83.34%, respectively. The AUC, sensitivity, specificity and accuracy of MFI were 86.29%, 70.51%, 87.10% and 85.56%, respectively. The AUC, sensitivity, specificity and accuracy of CEUS were 90.84%, 88.46%, 74.19% and 89.16%, respectively. The AUC, sensitivity, specificity and accuracy of the combined diagnosis of UE, MFI, and CEUS were 93.90%, 85.90%, 90.32%, and 92.07%, respectively. CONCLUSIONS: The combination of UE, CEUS and MFI has the highest specificity and accuracy in the differential diagnosis of benign and malignant breast lesions compared to any one used singly.

Evaluation of the Stiffness of Tissues Surrounding Thyroid Nodules with Shear Wave Elastography.

OBJECTIVES: This study evaluated the stiffness of tissue surrounding thyroid nodules using shear wave elastography (SWE). METHODS: A total of 128 thyroid nodules in 108 patients were examined with conventional ultrasound imaging and SWE. The maximum Young modulus value was measured to evaluate the stiffness of the thyroid nodules (E) and the 2-mm perinodular region (Eshell ). The number of thyroid fibrocytes was evaluated by Masson trichrome staining and image-processing software. The arrangement of the fibrous structure was also classified. RESULTS: The mean age ± SD of the 108 patients was 33.12 ± 13.34 years (range, 18-80 years). Thirty-nine thyroid nodules were classified as benign and 89 as malignant. Eshell was significantly higher for malignant nodules (95.0 ± 21.9 kPa) compared with benign nodules (48.1 ± 17.0 kPa; P < .001). Eshell yielded an area under the receiver operator characteristic curve value of 0.951, which was used for the diagnosis of nodules. There was a high positive correlation between E and Eshell in the malignant group (R = 0.722; P < .001) and a moderate positive correlation in the benign group (R = 0.601; P < .001). Percentages of fibrocytes correlated highly with Eshell in all samples as well as in malignant samples (R = 0.867 and R = 0.729, respectively; P < .001). The degree of disorder of the tissue surrounding thyroid nodules was positively correlated with Eshell (R = 0.833). CONCLUSIONS: Perinodular stiffness has potential to improve diagnosis of thyroid nodules.

The synergistic bactericidal effect of vancomycin on UTMD treated biofilm involves damage to bacterial cells and enhancement of metabolic activities.

In this study, the synergistic effect of vancomycin, a cell wall synthesis inhibitor, and ultrasound-targeted microbubble destruction (UTMD), on cell viability of Staphylococcus epidermidis, embedded in biofilm, was investigated. Biofilms are the leading causes of antibiotic-resistant bacterial infections of medical implants and prosthetics worldwide. The antibiotic-resistant nature of biofilm-embedded pathogens poses a critical challenge to the medical community. Previously, studies have demonstrated the efficacy of using ultrasound waves and UTMD in circumventing this problem. However, the mechanism(s) underlying this phenomenon was not clear. Here, the present study showed that both ultrasound and UTMD damaged the cell wall structure of S. epidermidis, and floccules and fragments from damaged cells were observed on transmission electron microscope micrograph. However, the cell membrane integrity was not seriously affected by treatments, and the treatment increased the metabolic activity levels of the dormant biofilm-embedded bacteria, detected by confocal laser scanning microscope and flow cytometry, which could make them susceptible to the effect of the antibiotic. Thus, the biological mechanism underlying the efficacy of the combined treatment involving UTMD and vancomycin in the case of S. epidermidis biofilm was dissected, which may be utilized for further investigations on other biofilm pathogens before clinical use.

Ultrasound microbubbles enhance human ß-defensin 3 against biofilms.

BACKGROUND: The infection of orthopedic implantation devices with Staphylococcus has been a serious concern within the biomaterial community. Treatments are not always successful because of antibiotic-resistant bacteria biofilm infection. Recent studies have shown that combination of antibiotics with low-frequency ultrasound (US) can enhance the bactericidal activity effectively against the formation of biofilms in vitro pilot study. Meanwhile, microbubbles evolved as targeted drug-delivery agents can provide nuclei for inertial cavitation and lower the threshold for US-induced cavitation. Human ß-defensin 3 (HBD-3) is a cationic antimicrobial peptide considered particularly promising for future bactericidal employment and has effect on antibiotic-resistant Staphylococcus biofilms. But the effect has not been reported when combined with US-targeted microbubble destruction (UTMD) in vivo. METHODS: In this study, we evaluated the effect of HBD-3 combined with UTMD on two tested Staphylococcus by the spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy, and real-time polymerase chain reaction. RESULTS: In the study, we found that the biofilm densities, the percentage of live cells, and the viable counts of two tested Staphylococcus that recovered from the biofilm on the titanium surface in mice were significantly decreased in the group of the HBD-3 combined with UTMD, compared with those of other groups. Furthermore, in the experiment, we found out that UTMD could enhance HBD-3 activity, which inhibits the biofilm-associated genes expression of icaAD and the methicillin-resistance genes expression of MecA by promoting the icaR expression simultaneously. CONCLUSIONS: The combination of HBD-3 with UTMD can play a significant role on the elimination of the antibiotic-resistant Staphylococcus biofilms in vivo.

Risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children.

OBJECTIVES: The aim of this study was to explore the risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children. METHODS: We retrospectively reviewed the medical records and sonograms of 288 cases of intussusception over a 3-year period. Logistic regression was used for the analysis of the clinical data (sex, age, duration of symptoms, and presence or absence of emesis or bloody stool) and sonographic features (initial location and intussusception length, presence or absence of free peritoneal fluid, and trapped fluid in the intussusception). RESULTS: The sex, age, and duration of symptoms showed no significant impact on the hydrostatic reducibility. The success rate became significantly lower for the intussusception cases with the presence of bloody stool, free peritoneal fluid, and trapped fluid in the intussusception (P < .05). The success rate was also lower when the intussusceptions were located in the left side of the abdomen (P < .05). For the above risk factors, the odds ratios from multivariate logistic regression analysis were 174.68 for initial intussusception location in the descending colon/rectum, 36.06 for the presence of peritoneal fluid, 13.22 for trapped fluid in the intussusception, and 9.27 for the presence of bloody stool. CONCLUSIONS: An initial intussusception location in the descending colon/rectum, the presence of peritoneal fluid, trapped fluid in the intussusception, and bloody stool are the most important risk factors for failure of sonographically guided saline hydrostatic intussusception reduction.

Efficacy of novel antibacterial compounds targeting histidine kinase YycG protein.

Treating staphylococcal biofilm-associated infections is challenging. Based on the findings that compound 2 targeting the HK domain of Staphylococcus epidermidis YycG has bactericidal and antibiofilm activities against staphylococci, six newly synthesized derivatives were evaluated for their antibacterial activities. The six derivatives of compound 2 inhibited autophosphorylation of recombinant YycG' and the IC50 values ranged from 24.2 to 71.2 µM. The derivatives displayed bactericidal activity against planktonic S. epidermidis or Staphylococcus aureus strains in the MIC range of 1.5-3.1 µM. All the derivatives had antibiofilm activities against the 6- and 24-h biofilms of S. epidermidis. Compared to the prototype compound 2, they had less cytotoxicity for Vero cells and less hemolytic activity for human erythrocytes. The derivatives showed antibacterial activities against clinical methicillin-resistant staphylococcal isolates. The structural modification of YycG inhibitors will assist the discovery of novel agents to eliminate biofilm infections and multidrug-resistant staphylococcal infections.

Role of Rot in bacterial autolysis regulation of Staphylococcus aureus NCTC8325.

Autolysis is an important process in cell wall turnover in Staphylococcus aureus, performed by several peptidoglycan hydrolases or so-called autolysins and controlled by many regulators. Rot is a global regulator that regulates numerous virulence genes, including genes encoding lipase, hemolysins, proteases and genes related to cell surface adhesion. The aim of our study was to determine whether Rot has the ability to regulate autolysis. We compared Triton-X-100-induced autolysis of S. aureus NCTC8325 and its rot knock-out mutant. We found that the rot mutant showed increased autolysis rates. By examining the transcript level of several autolysins and some known regulators responsible for regulating autolysis using real-time RT-PCR assays, we found that transcription of two autolysins (lytM, lytN) and one regulatory operon (lrgAB) was changed in the rot mutant. An in vitro approach was undertaken to determine which of these genes are directly controlled by Rot. Rot proteins were overproduced in Escherichia coli and purified. Gel mobility shift DNA binding assays were used and showed that in-vitro-purified Rot can directly bind to the promoter region of lytM, lytN, lrgA and lytS. We also tested biofilm formation of the rot mutant, and it showed enhancement in biofilm formation. Taken together, our results reveal that Rot affects autolysis by directly regulating autolysins LytM and LytN, and, via a regulatory system, LrgAB.

Ultrasound-targeted microbubble destruction enhances human ß-defensin 3 activity against antibiotic-resistant Staphylococcus biofilms.

The infection of orthopedic implantation devices with Staphylococcus is a serious concern within the biomaterial community. Treatments are not always successful because of antibiotic-resistant bacteria and serious biofilm infections. Human ß-defensin 3 (hBD-3) is considered to be the most promising class of defensin antimicrobial peptides and its effect on antibiotic-resistant Staphylococcus biofilms, combined with ultrasound (US)-targeted microbubble (MB) destruction (UTMD), has not been reported. In the study, we found that biofilm densities, the percentage of live cells and the viable counts of two tested Staphylococcus recovered from the biofilm were significantly decreased in the maximum concentration hBD-3 combined with UTMD compared with those of any other groups. Furthermore, results suggested that UTMD could also enhance 1MIC hBD-3 activity inhibiting the biofilm-associated genes expression of icaAD and the methicillin-resistance genes expression of MecA by simultaneously promoting the icaR expression. UTMD may have great potential for improving antibiotic activity against biofilm infections.