Electric Field-Assisted Agglomeration of Trace Nanoparticle Impurities for Ultrahigh Purity Chemicals.

With the advancement of semiconductor manufacturing technology, the effects of trace impurities in industrial chemicals have grown significantly. In industrial processes, conventional purification methods, such as filtration and distillation, have reached their limits for removing nanoparticles from aqueous and acidic solutions. Especially, silicon and silicate are two fundamental byproducts in semiconductor fabrication processes. Assembly and subsequent removal of these materials at the nanoparticle level have been confronted with significant challenges. Therefore, it is imperative to develop technologies to effectively control and remove these impurities for next-generation manufacturing processes. In this study, we explored the use of electric field-assisted assembly to agglomerate silicate and silicon nanoparticles in industry-standard aqueous and acidic solutions. By applying an alternating current electric field, we induced dipole moments in the nanoparticles, which led to their agglomeration. Notably, nanoparticles smaller than 4 nm grew into significantly larger ones, with submicroparticle sizes exceeding 87 nm for silicate and reaching 130 nm for silicon. Through systematic analysis of the size distribution changes, we identified optimal agglomeration times of 10 min for silicate and 20 min for silicon, revealing effective agglomeration within the frequency range of 1-1000 kHz. The agglomerated particles were stable for 5 days. Our electric field-assisted approach to obtain assembled nanoparticles that can be subsequently removed by conventional purification processes holds promise for enhancing future microfabrication processes, such as semiconductor manufacturing, potentially improving the manufacturing yield and uniformity by reducing the number of trace particles that can act as defective sites.

Val43 residue of NsrR is crucial for the nitric oxide response of Salmonella Typhimurium.

ABSTRACT: In pathogenic bacteria, the flavohemoglobin Hmp is crucial in metabolizing the cytotoxic levels of nitric oxide (NO) produced in phagocytic cells, contributing to bacterial virulence. Hmp expression is predominantly regulated by the Rrf2 family transcription repressor NsrR in an NO-dependent manner; however, the underlying molecular mechanism in enterobacteria remains poorly understood. In this study, we identified Val43 of Salmonella Typhimurium NsrR (StNsrR) as a critical amino acid residue for regulating Hmp expression. The Val43-to-Ala-substituted mutant NsrR isolated through random and site-directed mutagenesis showed high binding affinity to the target DNA irrespective of NO exposure, resulting in a severe reduction in hmp transcription and slow NO metabolism in Salmonella under NO-producing conditions. Conversely, the Val43-to-Glu-substituted NsrR caused effects similar to nsrR null mutation, which directed hmp transcription and NO metabolism in a constitutive way. Comparative analysis of the primary sequences of NsrR and another NO-sensing Rrf2 family regulator, IscR, from diverse bacteria, revealed that Val43 of enterobacterial NsrR corresponds to Ala in Pseudomonas aeruginosa or Streptomyces coelicolor NsrR and Glu in enterobacterial IscR, all of which are located in the DNA recognition helix α3. The predicted structure of StNsrR in complex with the hmp DNA suggests dissimilar spatial stoichiometry in the interactions of Val43 and its substituted residues with the target DNA, consistent with the observed phenotypic changes in StNsrR Val43 mutants. Our findings highlight the discriminative roles of the NsrR recognition helix in regulating species-specific target gene expression, facilitating effective NO detoxification strategies in bacteria across diverse environments. IMPORTANCE: The precise regulation of flavohemoglobin Hmp expression by NsrR is critical for bacterial fitness, as excessive Hmp expression in the absence of NO can disturb bacterial redox homeostasis. While the molecular structure of Streptomyces coelicolor NsrR has been recently identified, the specific molecular structures of NsrR proteins in enterobacteria remain unknown. Our discovery of the crucial role of Val43 in the DNA recognition helix α3 of Salmonella NsrR offers valuable insights into the Hmp modulation under NO stress. Furthermore, the observed amino acid polymorphisms in the α3 helices of NsrR proteins across different bacterial species suggest the diverse evolution of NsrR structure and gene regulation in response to varying levels of NO pressure within their ecological niches.

Low frequency changes in CO2 concentration in East Asia related to Pacific decadal oscillation and Atlantic multi-decadal oscillation for mid-summer and early fall.

The climatological seasonal maximum and minimum CO2 concentrations in East Asia for 1987-2020 have been recorded at April and August, respectively. We found that the CO2 concentration in East Asia during July, August, and September (JAS) is lower than normal before the late 1990s and after the early 2010s (Low_CO2 period), and higher than normal from the late 1990s to the early 2010s (High_CO2 period). The low-frequency variability of CO2 concentration in East Asia during JAS correlates with both Pacific Decadal Oscillation (PDO) and Atlantic Multi-decadal Oscillation (AMO)-related sea surface temperatures (SSTs). We analyzed atmospheric and oceanic conditions during JAS between the two periods, finding that precipitation in East Asia decreased during JAS in High_CO2 period than that in Low_CO2 period, possibly due to PDO and AMO-related SST forcing, which decreases vegetation's photosynthetic activity. This may lead to a higher CO2 concentration than normal in East Asia in High_CO2 period through reduced uptake of CO2 from the atmosphere. This implies that terrestrial vegetation activity influenced by remote SST forcings should be monitored to better understand regional carbon cycles in East Asia.

Hexane extract of green tea (Camellia sinensis) leaves is an exceptionally rich source of squalene.

Squalene is a cancer chemo-preventive and skin protective agent with high commercial demand. Here, we report for the first time that the green tea (Camellia sinensis) leaves is a surprisingly rich plant-based source of squalene. Young and tender leaves and old and turf leaves were collected at four different collecting seasons (April-August). Lipophilic compounds in the leaves and commercial green teas were extracted with hexane. The squalene contents in the hexane extracts varied greatly with the types of the leaves and collecting seasons. The hexane extract of turf leaves contained significantly higher contents of squalene than the extract of tender leaves. The hexane extract of the turf leaves collected in August contained the highest content of squalene (29.2 g/kg extract). This represents the first report on the qualitative and quantitative information on squalene in green tea leaves.

Comparison of One- and Two-Region of Interest Strain Elastography Measurements in the Differential Diagnosis of Breast Masses.

OBJECTIVE: To compare the diagnostic performance and interobserver variability of strain ratio obtained from one or two regions of interest (ROI) on breast elastography. MATERIALS AND METHODS: From April to May 2016, 140 breast masses in 140 patients who underwent conventional ultrasonography (US) with strain elastography followed by US-guided biopsy were evaluated. Three experienced breast radiologists reviewed recorded US and elastography images, measured strain ratios, and categorized them according to the American College of Radiology breast imaging reporting and data system lexicon. Strain ratio was obtained using the 1-ROI method (one ROI drawn on the target mass), and the 2-ROI method (one ROI in the target mass and another in reference fat tissue). The diagnostic performance of the three radiologists among datasets and optimal cut-off values for strain ratios were evaluated. Interobserver variability of strain ratio for each ROI method was assessed using intraclass correlation coefficient values, Bland-Altman plots, and coefficients of variation. RESULTS: Compared to US alone, US combined with the strain ratio measured using either ROI method significantly improved specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve (AUC) (all p values < 0.05). Strain ratio obtained using the 1-ROI method showed higher interobserver agreement between the three radiologists without a significant difference in AUC for differentiating breast cancer when the optimal strain ratio cut-off value was used, compared with the 2-ROI method (AUC: 0.788 vs. 0.783, 0.693 vs. 0.715, and 0.691 vs. 0.686, respectively, all p values > 0.05). CONCLUSION: Strain ratios obtained using the 1-ROI method showed higher interobserver agreement without a significant difference in AUC, compared to those obtained using the 2-ROI method. Considering that the 1-ROI method can reduce performers' efforts, it could have an important role in improving the diagnostic performance of breast US by enabling consistent management of breast lesions.

Synthesis and formation mechanism of bone mineral, whitlockite nanocrystals in tri-solvent system.

Whitlockite (WH, Ca18Mg2(HPO4)2(PO4)12) is the second most abundant bone mineral and has attracted attention as one of the novel bone regenerative materials. It has proven to enhance growth and promote osteogenesis of stem cells. However, investigating the mechanism of formation of pure phase WH nanocrystals remains a challenge. In this study, we introduced an interesting synthesis approach of WH nanocrystals using a tri-solvent system for the solid-liquid-solution (SLS) process. The ratio of precursor and reaction solvent composition was optimized to generate WH nanocrystals with tunable size, morphology (nanoplates, nanospheres), and surface properties (hydrophobic, hydrophilic), which is impossible to achieve using the traditional precipitation method. Molecular dynamics (MD) simulations revealed that the growth direction of nanoplates is highly related to the surfactant and its binding affinity. Finite element method (FEM) simulations elucidated that the ratio of ethanol/water plays an important role in defining the crystallinity and morphology of WH. In this study, we demonstrated that the cell proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is enhanced upon treatment with WH. The results of quantitative real-time polymerase chain reaction (qPCR) revealed that WH can positively accelerate the osteogenic differentiation in hBMSCs. The as-synthesized WH has a great potential in the future to be used in osteogenic tissue engineering. This study opens a new horizon for the synthesis and application of WH.

The Small Protein CydX Is Required for Cytochrome bd Quinol Oxidase Stability and Function in Salmonella enterica Serovar Typhimurium: a Phenotypic Study.

Cytochrome bd quinol oxidases, which have a greater affinity for oxygen than heme-copper cytochrome oxidases (HCOs), promote bacterial respiration and fitness in low-oxygen environments, such as host tissues. Here, we show that, in addition to the CydA and CydB subunits, the small protein CydX is required for the assembly and function of the cytochrome bd complex in the enteric pathogen Salmonella enterica serovar Typhimurium. Mutant S Typhimurium lacking CydX showed a loss of proper heme arrangement and impaired oxidase activity comparable to that of a ΔcydABX mutant lacking all cytochrome bd subunits. Moreover, both the ΔcydX mutant and the ΔcydABX mutant showed increased sensitivity to ß-mercaptoethanol and nitric oxide (NO). Cytochrome bd-mediated protection from ß-mercaptoethanol was not a result of resistance to reducing damage but, rather, was due to cytochrome bd oxidase managing Salmonella respiration, while ß-mercaptoethanol interacted with the copper ions necessary for the HCO activity of the cytochrome bo-type quinol oxidase. Interactions between NO and hemes in cytochrome bd and cytochrome bd-dependent respiration during nitrosative stress indicated a direct role for cytochrome bd in mediating Salmonella resistance to NO. Additionally, CydX was required for S Typhimurium proliferation inside macrophages. Mutants deficient in cytochrome bd, however, showed a significant increase in resistance to antibiotics, including aminoglycosides, d-cycloserine, and ampicillin. The essential role of CydX in cytochrome bd assembly and function suggests that targeting this small protein could be a useful antimicrobial strategy, but potential drug tolerance responses should also be considered.IMPORTANCE Cytochrome bd quinol oxidases, which are found only in bacteria, govern the fitness of many facultative anaerobic pathogens by promoting respiration in low-oxygen environments and by conferring resistance to antimicrobial radicals. Thus, cytochrome bd complex assembly and activity are considered potential therapeutic targets. Here we report that the small protein CydX is required for the assembly and function of the cytochrome bd complex in S Typhimurium under stress conditions, including exposure to ß-mercaptoethanol, nitric oxide, or the phagocytic intracellular environment, demonstrating its crucial function for Salmonella fitness. However, cytochrome bd inactivation also leads to increased resistance to some antibiotics, so considerable caution should be taken when developing therapeutic strategies targeting the CydX-dependent cytochrome bd.

Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.

OBJECTIVES: This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO). BACKGROUND: CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial. METHODS: The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis). RESULTS: Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors. CONCLUSIONS: Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

A computer-aided diagnosis system using artificial intelligence for the diagnosis and characterization of breast masses on ultrasound: Added value for the inexperienced breast radiologist.

To evaluate the value of the computer-aided diagnosis (CAD) program applied to diagnostic breast ultrasonography (US) based on operator experience.US images of 100 breast masses from 91 women over 2 months (from May to June 2015) were collected and retrospectively analyzed. Three less experienced and 2 experienced breast imaging radiologists analyzed the US features of the breast masses without and with CAD according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon and categories. We then compared the diagnostic performance between the experienced and less experienced radiologists and analyzed the interobserver agreement among the radiologists.Of the 100 breast masses, 41 (41%) were malignant and 59 (59%) were benign. Compared with the experienced radiologists, the less experienced radiologists had significantly improved negative predictive value (86.7%-94.7% vs 53.3%-76.2%, respectively) and area under receiver operating characteristics curve (0.823-0.839 vs 0.623-0.759, respectively) with CAD assistance (all P < .05). In contrast, experienced radiologists had significantly improved specificity (52.5% and 54.2% vs 66.1% and 66.1%) and positive predictive value (55.6% and 58.5% vs 64.9% and 64.9%, respectively) with CAD assistance (all P < .05). Interobserver variability of US features and final assessment by categories were significantly improved and moderate agreement was seen in the final assessment after CAD combination regardless of the radiologist's experience.CAD is a useful additional diagnostic tool for breast US in all radiologists, with benefits differing depending on the radiologist's level of experience. In this study, CAD improved the interobserver agreement and showed acceptable agreement in the characterization of breast masses.

Heat-induced conversion of gingerols to shogaols in ginger as affected by heat type (dry or moist heat), sample type (fresh or dried), temperature and time.

The impact of heat type, sample type, temperature and time on the heat-induced conversion of gingerols to shogaols in ginger were studied by an UHPLC-ESI-MS/MS. Heat treatments greatly induced the conversion of gingerols to shogaols in ginger. As the temperature increased, the faster conversion of gingerols into shogaols were observed. However, the efficiency of the heat-induced conversion differed greatly with the heat types. Moist heat treatment induced significantly higher quantity of shogaols than dry heat treatment. The moist heat treatment at 120 °C for 360 min induced the highest conversion, reaching to 2991 mg 6-shogaol per kg ginger. In addition, dry-heat induced conversion was affected by the sample type. The dry-heat treatment on dried powder induced significantly higher quantity of shogaols than that on sliced fresh ginger. This represents the first systematic comparative study on the heat and sample types on the heat-induced conversion of gingerols into shogaols in ginger.

Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype.

This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for ≥2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4-21.8%) and 71.4% (95% CI = 45.7-86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.

Early stimulated thyroglobulin for response prediction after recombinant human thyrotropin-aided radioiodine therapy.

OBJECTIVE: Measurement of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) is generally recommended 72 h after the second rhTSH injection. However, due to the acute effect of I-131 on thyrocytes, Tg measured after radioiodine therapy (RIT) would not accurately reflect the thyroid tissue burden. We aimed to determine predictive values of serum Tg level measured just before rhTSH-aided RIT and to compare the results obtained just after RIT in patients with differentiated thyroid carcinoma (DTC). METHODS: We evaluated 150 patients with DTC who underwent rhTSH-aided RIT (2.96-6.66 GBq) after total thyroidectomy between 2009 and 2014. Serum Tg level was measured 24 h (early Tg) and 72 (or 96) h (delayed Tg) after the second rhTSH injection. An excellent response was defined based on the latest American Thyroid Association Guidelines. Univariate and multivariate analyses were performed for early Tg, delayed Tg, and other clinical variables. RESULTS: In the multivariate analysis, tumor size [odds ratio (OR) 1.716; 95% confidence interval (CI) 1.019-2.882; p = 0.042] and early Tg level (OR 2.012; 95% CI 1.384-2.925, p < 0.001) independently predicted excellent responses. The cutoff for the best early Tg level to predict a non-excellent response was 2.0 ng/mL. Delayed Tg was not a significant predictor (OR 0.992; 95% CI 0.969-1.015; p = 0.492). CONCLUSIONS: Early stimulated Tg significantly predicted therapeutic response after rhTSH-aided RIT in patients with DTC. Therefore, serum Tg should be measured before RIT to predict therapeutic responses.

One step salting-out assisted liquid-liquid extraction followed by UHPLC-ESI-MS/MS for the analysis of isoflavones in soy milk.

We developed and validated a fast UHPLC-ESI-MS/MS in combination with one step salting-out assisted liquid-liquid extraction (SALLE) for high throughput analysis of 12 isoflavones in soy milks. Conventional sample preparation requires two steps composing time-consuming freeze-drying (72h) and solvent extraction (2h). The SALLE required only about 40min, which was over 100times faster without compromising the extraction efficiency. The baseline separation of 12 isoflavones was achieved in 2.5min by the UHPLC-MS/MS which is the fastest chromatographic method ever reported. The new method was fast, simple, selective, sensitive, precise and accurate. The method was successfully applied to 22 commercial soy milks for the high throughput analysis of isoflavones. The new method would be a fast, simple, reliable, and useful measure for the analysis of isoflavones in soy milk especially in the laboratories facing the challenges of saving the analytical time, labor cost and solvent usage.

5-Hydroxymethylcytosine correlates with epigenetic regulatory mutations, but may not have prognostic value in predicting survival in normal karyotype acute myeloid leukemia.

Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated. The median 5hmC level was 0.065% (range 0.001-0.999). Mutation rates were 13.1% for TET2mut, 6.7% for IDH1mut, and 13.9% for IDH2mut. The prevalence of TET2 and/or IDH1/2 was 33.1% (124/375). TET2 and IDH1/2 mutated patients had significantly lower levels of log(5hmC) compared with patients without TET2 or IDH1/2 mutations (p<0.001). With a median follow-up of 55.5 months (range, 0.7-179.8), there was no significant difference in overall survival, event-free survival, and relapse risk according to TET2mut or IDH1/2mut (all, p>0.05). To identify its prognostic value, we sub-classified the levels of 5hmC into tertiles for 5hmC values. However, there was no significant association between the categories of 5hmC levels and survival or relapse risk (all p>0.05). Patients with TET2 or IDH1/2 mutations had lower levels of 5hmC. The 5hmC levels may not be predictive of survival in patients with normal karyotype AML.

Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy.

Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; 37 patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified 5 distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy. This study demonstrates that patterns of mutation acquisition, persistence, and clearance vary but have a number of interesting correlations with clinical outcomes. Mutation burden often persisted despite successful TKI response (pattern 1), providing indirect evidence that these mutations also originated from preleukemic mutations, whereas patients exhibiting mutation clearance (pattern 3) showed mixed clinical outcomes. Unsurprisingly, patients acquiring new mutations during treatment failed TKI therapy (pattern 2). These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms. In summary, clinical implications of mutation profiles and dynamics in CML should be interpreted with caution.

Coronary flow reserve and relative flow reserve measured by N-13 ammonia PET for characterization of coronary artery disease.

OBJECTIVE: We evaluated the relationships between coronary flow reserve (CFR) and relative flow reserve (RFR) measured by N-13 ammonia positron emission tomography (PET) for characterization of epicardial coronary artery disease (CAD). METHODS: Sixty-nine consecutive stable angina patients underwent N-13 ammonia PET, coronary computed tomography angiography (CCTA), and if necessary, invasive coronary angiography (CAG) within 2 weeks. Myocardial blood flow (MBF), CFR, RFR, and coronary vascular resistance of the reference arterial territory (CVRref) were measured by N-13 ammonia PET. The presence of significant stenosis (SS) and diffuse atherosclerosis (DA) was evaluated on CCTA and CAG. Functional parameters measured by PET were compared among arteries with and without SS and DA. RESULTS: Arteries with SS and those with DA showed significantly lower stress MBF, as compared to those without. RFR was significantly lower in arteries with SS as compared to those without, while CFR was not. CFR was significantly lower in arteries with DA as compared to those without, while RFR was not. Among arteries without SS, CFR was significantly lower in those with DA as compared to those without. However, among arteries with SS, CFR was similar between those with and without DA. In contrast, RFR was significantly lower in arteries with SS, regardless of the presence of DA. CFR and RFR showed a weak positive correlation (r = 0.269) with discordance in 24 cases (35%). Among the arteries with CFR-RFR discordance, the prevalence of DA was significantly higher in those with low CFR but preserved RFR, as compared to those with preserved CFR but low RFR (75 vs 25%, p = 0.028). CVRref was significantly higher in arteries with DA, implicating a correlation of DA with underlying microvascular disease. CONCLUSIONS: CFR and RFR measured by myocardial perfusion PET could provide a comprehensive information for characterization of epicardial CAD.

Iodine Uptake Patterns on Post-ablation Whole Body Scans are Related to Elevated Serum Thyroglobulin Levels After Radioactive Iodine Therapy in Patients with Papillary Thyroid Carcinoma.

PURPOSE: Serum thyroglobulin (Tg) level is frequently elevated shortly after radioactive iodine (RAI) ablation therapy. The authors studied the relationship between the elevation of serum Tg after RAI therapy and iodine uptake pattern on post-ablation whole body scans (RxWBSs) in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: The study subjects were patients with PTC that had undergone first RAI therapy with thyroid hormone withdrawal after total thyroidectomy. Patients with a high level of serum anti-Tg antibody (TgAb, ≥ 60 U/mL), possible regional or distant metastasis as determined by pre-ablation or post-ablation studies, and negative iodine uptake of the anterior neck on RxWBS were excluded. Serum Tg was checked twice, that is, 7 days after (post-ablation Tg) and on the day of RAI therapy (pre-ablation Tg). Ratio of pre-ablation Tg to post-ablation Tg (Tg ratio) was used to assess changes in serum Tg levels after RAI therapy. Patients were classified into two groups according to the presence of midline uptake above the thyroidectomy bed on RxWBS (negative (group 1) or positive (group 2) midline uptake). Variables were subjected to analysis to identify differences between the two groups. RESULTS: Two hundred and fifty patients were enrolled in this study; 101 in group 1 and 149 in group 2. Based on univariate analysis, post-ablation Tg (8.12 ± 11.05 vs. 34.12 ± 54.31; P < 0.001) and Tg ratio (7.81 ± 8.98 vs. 20.01 ± 19.84; P < 0.001) were significantly higher in group 2. On the other hand, gender, tumor (T) stage, lymph node (N) stage, size, multiplicity or bilaterality of primary tumor, dose of 131I, serum TgAb and thyroid-stimulating hormone (TSH) level (before or after RAI therapy) were not significantly different in the two groups. Variables with P values of < 0.25 by univariate analysis were subjected to multivariate analysis, which showed post-ablation Tg (OR 1.060, 95 % CI = 1.028-1.092; P < 0.001) and Tg ratio (OR 1.059, 95 % CI = 1.028-1.092; P = 0.001) were significantly higher in group 2. CONCLUSION: Serum Tg level after RAI therapy was significantly higher in patients with midline uptake on RxWBS, compared with patients without midline uptake on RxWBS. Further investigations are needed to reveal the correlation between serum Tg elevation and clinical outcome according to the presence of midline uptake.

Giant Cell Tumor with Secondary Aneurysmal Bone Cyst Shows Heterogeneous Metabolic Pattern on 18F-FDG PET/CT: A Case Report.

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on 18F-FDG PET/CT.

Concurrent Treatment with Taxifolin and Cilostazol on the Lowering of ß-Amyloid Accumulation and Neurotoxicity via the Suppression of P-JAK2/P-STAT3/NF-κB/BACE1 Signaling Pathways.

Taxifolin is a potent flavonoid that exerts anti-oxidative effect, and cilostazol increases intracellular cAMP levels by inhibiting phosphodiesterase 3 that shows antiinflammatory actions. BACE1 (ß-site APP cleaving enzyme 1) is the rate-limiting enzyme responsible for the ß-cleavage of amyloid precursor proteins to Aß peptides. In this study, endogenous Aß and C99 accumulation was explored in N2a Swe cells exposed to 1% FBS medium. Increased Aß and C99 levels were significantly attenuated by taxifolin alone and in combination with cilostazol. Increased phosphorylated JAK2 at Tyr1007/1008 (P-JAK), phosphorylated STAT3 at Tyr 705 (P-STAT3) expressions and increased expressions of BACE1 mRNA and protein in the activated N2a Swe cells were significantly attenuated by taxifolin (10~50 µM), cilostazol (10~50 µM) alone and in combination at minimum concentrations. In these cells, decreased cytosol IκBα expression was elevated, and increased nuclear NF-κB p65 level and nuclear NF-κB p65 DNA binding activity were significantly reduced by taxifolin and cilostazol in a similar manner. Following STAT3 gene (~70% reduction) knockdown in N2a cells, Aß-induced nuclear NF-κB and BACE1 expressions were not observed. Taxifolin, cilostazol, or resveratrol significantly stimulated SIRT1 protein expression. In SIRT1 gene-silenced (~50%) N2a cells, taxifolin, cilostazol, and resveratrol all failed to suppress Aß1-42-stimulated P-STAT3 and BACE1 expression. Consequently, taxifolin and cilostazol were found to significantly decrease lipopolysaccharide (1-10 µg/ml)-induced iNOS and COX-2 expressions, and nitrite production in cultured BV-2 microglia cells and to increase N2a cell viability. In conclusion, taxifolin and cilostazol strongly inhibited amyloidogenesis in a synergistic manner by suppressing P-JAK2/P-STAT3-coupled NF-κB-linked BACE1 expression via the up-regulation of SIRT1.

Open-Mouth Bone Scintigraphy Is Better than Closed-Mouth Bone Scintigraphy in the Diagnosis of Temporomandibular Osteoarthritis.

PURPOSE: Closed-mouth bone scintigraphy (CM scan) and closed-mouth single-photon emission computed tomography (CM SPECT) are used for conventional evaluation of osteoarthritis of the temporomandibular joint (TMJ). However, the adequacy of open-mouth bone scintigraphy (OM scan) has not yet been evaluated. Therefore, the purpose of this study was to compare the diagnostic performance of CM scan, CM SPECT, and OM scan. METHODS: Thirty-six patients with suspicion of an abnormality of the TMJ and who underwent a (99m)Tc-HDP CM scan, CM SPECT, and an OM scan were enrolled. The scans were assessed visually for the presence of positive focal uptake in the TMJ. Osteoarthritis was defined as arthralgia plus crepitus or radiologic signs of arthrosis. RESULTS: Of 72 TMJs, 21 (29.2 %) were diagnosed with osteoarthritis. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 90.5 %, 49.0 %, 42.2 %, 92.6 % and 61.1 % for the CM scan, 81.0 %, 58.8 %, 44.7 %, 88.2 % and 65.3 % for CM SPECT, and 81.0 %, 82.4 %, 65.4 %, 91.3 % and 81.9 % for the OM scan, respectively. The accuracy of the OM scan was higher than that of CM SPECT and the CM scans (p = 0.004 and p < 0.001, respectively). CONCLUSIONS: The OM scan was more accurate than the conventional CM scan and even CM SPECT for diagnosing TMJ osteoarthritis.