Therapeutic efficacy and safety of home-based portable laser irradiation on patients with wrist pain: a single-blinded randomized controlled trial.

The purpose of this study is to confirm the effect of small, portable low-level laser therapy (light sources in square configuration: 830 nm GaAs diode 3.2 mW at the center, 4 × 650 nm InGaAIP diodes over the corners) treatment in reducing and enhancing hand function in patients with wrist pain. This study was a prospective, randomized, sham-controlled, and home-based self-therapy trial. A total of thirty subjects with wrist pain were enrolled. All participants received low-level laser therapy on painful area at the wrist. The experimental group (n = 15) received laser stimulation, while the control group (n = 15) received sham stimulation using identical equipment that generated only a red light without the laser output. Both groups self-treated for 30 min a day, 5 days per week for 3 weeks, total of 15 sessions. The primary outcome was assessed using a visual analogue scale (VAS) for wrist pain from 0 (painless) to 10 (extreme pain). The secondary outcomes were measured with patient-rated wrist evaluation (PRWE), grip strength, lateral, palmar, and tip pinch strength. Measures were taken before and after treatment. A total of thirty participants provided outcome data. After the intervention, both groups showed a significant decrease in VAS score, from 4.93 to 3.67 in experimental group, from 5.53 to 4.00 in control group (the experiment group: p = 0.020, the control group: p = 0.003). The experimental group showed a significant improvement in function scale score (p = 0.012), the control group did not. Lateral and pinch strength was significantly improved in the experimental group (p = 0.017) and in the control group (p = 0.034) respectively. There were no side effects in the patients. Medical laser irradiation is a portable and easy-to-use laser irradiator without side effects. Clinical Trial Registration number: KCT0006604.

Effect of headspace gas composition in kimchi packaging on the quality characteristics of kimchi.

This study evaluated the effects of gas composition in kimchi packaging on kimchi quality. Completely sealed packaging without gas inflow/outflow during fermentation (S1), packaging allowing gas outflow (S2), and packaging allowing gas inflow and outflow (S3) were used. Microbial composition analysis, volatile compound content analysis, and sensory evaluation were performed to determine the differences in kimchi quality among samples. Metabolites were examined using principal component analysis. Gas composition analysis showed that the ratio of CO2 increased during the storage period in S1, the ratio of nitrogen and CO2 contents was constant in S2, and the ratio of oxygen was significantly higher in S3. No significant differences in the lactic acid bacteria number were observed. However, coliforms were only detected in S3, and yeast and mold proliferated faster in S3 than in S2 or S1. The main compounds detected in S1 and S2 were alcohols, whereas those in S3 were esters such as ß-phenethyl acetate produced by yeast. Sensory evaluation showed that S3 had the lowest odor, taste, and overall scores, whereas S2 had the highest. In conclusion, the gas composition inside the kimchi package greatly affects the quality of kimchi. Our findings provide important data that can be useful in the manufacture of commercial kimchi. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05795-z.

Effect of the addition of maltodextrin on metabolites and microbial population during kimchi fermentation.

Gelatinized starch sauce, one of the sub-ingredients have been widely used in kimchi for their roles in increasing viscosity of kimchi seasoning, and fermentation. Gelatinized glutinous rice (GGR), which is one of the most used starch sources in kimchi preparation. However, GGR is accelerated to the fermentation process but lead to a reduction in the shelf life of the kimchi. Therefore, in this study, we demonstrate the effectiveness of using maltodextrin (MD) as a novel starch source instead of GGR to slow down the rate of kimchi fermentation. The properties of the kimchi with MD and GGR fermentation (free sugar content, organic acid content, pH, and acidity) as well as their microbial growth rates after 12 days of fermentation were compared. After fermentation of 12 days, the free sugar of GGR-kimchi (GGRK) increased more rapidly than those of MD-kimchi (MDK), while higher sugar alcohol (mannitol) and organic acid contents were observed for GGRK than for MDK. Furthermore, initial aerobic and lactic acid bacteria counts were higher for GGRK than for MDK. These results indicate that fermentation proceeds at a slower rate in MDK than in GGRK, and they will provide a basis for further research into storage of kimchi. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05742-y.

Home-Based Transcranial Direct Current Stimulation to Enhance Cognition in Stroke: Randomized Controlled Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising tool for improving poststroke cognitive function. Home-based rehabilitation is increasingly required for patients with stroke, and additional benefits are expected if supplemented with remotely supervised tDCS (RS-tDCS). We evaluated the cognitive improvement effect and feasibility of RS-tDCS in patients with chronic stroke. METHODS: Twenty-six patients with chronic stroke and cognitive impairment (Korean version of the Montreal Cognitive Assessment [K-MoCA] score <26) were randomized into real and sham RS-tDCS groups and underwent concurrent computerized cognitive training and RS-tDCS. Patients and caregivers underwent training to ensure correct tDCS self-application, were monitored, and treated 5 d/wk for 4 weeks. We investigated several cognition tests including K-MoCA, Korean version of the Dementia Rating Scale-2, Korean-Boston Naming Test, Trail Making Test, Go/No Go, and Controlled Oral Word Association Test at the end of the training sessions and one month later. Repeated-measures ANOVA was used for comparison between the groups and within each group. The adherence rate of the appropriate RS-tDCS session was also investigated. RESULTS: In within-group comparison, unlike the sham group, the real group showed significant improvement in K-MoCA (Preal=0.004 versus Psham=0.132), particularly in patients with lower baseline K-MoCA (K-MoCA10-17; Preal=0.001 versus Psham=0.835, K-MoCA18-25; Preal=0.060 versus Psham=0.064) or with left hemispheric lesions (left; Preal=0.010 versus Psham=0.454, right; Preal=0.106 versus Psham=0.128). In between-group comparison, a significant difference was observed in K-MoCA in the lower baseline K-MoCA subgroup (K-MoCA10-17; Ptime×group=0.048), but no significant difference was found in other cognitive tests. The adherence rate of successful application of the RS-tDCS was 98.4%, and no serious adverse effects were detected. CONCLUSIONS: RS-tDCS is a safe and feasible rehabilitation modality for poststroke cognitive dysfunction. Specifically, RS-tDCS is effective in patients with moderate cognitive decline. Additionally, these data demonstrate the potential to enhance home-based cognitive training, although significant differences were not consistently found in between-group comparisons; therefore, further larger studies are needed. REGISTRATION: URL: https://cris.nih.go.kr; Unique identifier: KCT0003427.

Motor organization of unilateral polymicrogyria associated with ipsilateral brainstem atrophy - a case report.

BACKGROUND: Polymicrogyria refers to the disruption of normal cerebral cortical development late in neuronal migration or in early cortical organization. Although patients with polymicrogyria feature relatively favorable motor outcomes, polymicrogyric lesions accompanied by extensive unilateral hemispheric atrophy and ipsilateral brainstem atrophy may induce poorer motor outcomes. This study is the first to employ transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize changes to motor organization and white matter tracts induced by polymicrogyria. CASE PRESENTATION: We document a case of a 16-year-old female with left hemiplegic unilateral polymicrogyria associated with ipsilateral brainstem atrophy. Magnetic resonance imaging (MRI) of the brain revealed unilateral polymicrogyria to have affected anterior cortical areas, including the perisylvian region on the right side. The right halves of the brain and brainstem were significantly smaller than the left halves. Although our patient was found to exhibit cortical dysplasia of the right frontoparietal and sylvian fissure areas and a decreased number of fibers in the corticospinal tract (CST) of the affected side on DTI, the connectivity of the CST was preserved up to the motor cortex. We also measured the cross-sectional area of the CST at the level of the pons. In TMS, contralateral motor evoked potentials (MEPs) were evoked from both hands, but the ipsilateral MEPs were evoked only from the left hand. The left hand featured a long duration, polyphasic pattern of contralateral MEPs. DISCUSSION AND CONCLUSION: TMS revealed that the concurrent bilateral projections to the paretic hand from the affected and unaffected hemispheres and contralateral MEPs in the paretic hand were polyphasic, indicating delayed electrophysiological maturation or a pathologic condition of the corticospinal motor pathways. In DTI, the cross-sectional area of the CST at the level of the pons on the affected side was smaller than that on the unaffected side. These DTI findings reveal an inadequate CST volume. Despite extensive brain malformation and ipsilateral brainstem atrophy, our patient had less severe motor dysfunction and presented with involuntary mirror movements. Mirror movements in the paretic hand are considered to indicate ipsilateral corticospinal projections from the unaffected hemisphere and may suggest favorable motor outcomes in early brain injury.

Free-Living Amoeba Vermamoeba vermiformis Induces Allergic Airway Inflammation.

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/ E2). We axenically cultured KFA5 and KFA21. We applied approximately 1 × 106 to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4+ interleukin 4+ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

Effects of Low-Frequency Whole-Body Vibration on Muscle Activation, Fatigue, and Oxygen Consumption in Healthy Young Adults: A Single-Group Repeated-Measures Controlled Trial.

CONTEXT: Whole-body vibration (WBV) training improves muscle strength and balance. Few studies have focused on the effects of WBV frequencies below 30 Hz. We aimed to investigate the effect of low-frequency WBV training on muscle activity, fatigue recovery, and oxygen consumption (VO2). DESIGN: Prospective single-group, repeated-measures study. METHODS: In this controlled laboratory setting study, 20 healthy adults (age 23.26 [1.66] y) performed half squats at 0, 4, 6, 8, 12, 16, 20, 24, and 30-Hz WBV. Muscle activity was evaluated using the root mean square and peak electromyography amplitude of 6 muscles (iliocostalis, rectus abdominis, rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius) obtained via surface electromyography. VO2 was measured during the squats using a gas analyzer, and fatigue recovery was evaluated using measurements of lactate after the squats and after a recovery period. Statistical significance was set at P < .05, and analysis of variance was conducted to determine differences in muscle activity, fatigue, recovery, and VO2, with post hoc analyses as appropriate. RESULTS: Of the 6 muscles measured, the muscle activity of the gastrocnemius alone significantly increased from 0 Hz at 4, 8, 12, 16, 24, and 30 Hz based on the root mean square values and at 4, 8, 12, and 30 Hz based on the peak electromyography amplitude values. There were no significant differences in the other muscles. There were no significant differences in VO2 or in lactate levels. CONCLUSIONS: Low-frequency WBV during squat exercises significantly increased the activity of the gastrocnemius medialis only at specific frequencies in healthy young adults. Low-frequency WBV is safe and has the potential to increase muscle activity.

Prediction of prognostic signatures in triple-negative breast cancer based on the differential expression analysis via NanoString nCounter immune panel.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) is an aggressive and complex subtype of breast cancer. The current biomarkers used in the context of breast cancer treatment are highly dependent on the targeting of oestrogen receptor, progesterone receptor, or HER2, resulting in treatment failure and disease recurrence and creating clinical challenges. Thus, there is still a crucial need for the improvement of TNBC treatment; the discovery of effective biomarkers that can be easily translated to the clinics is essential. METHODS: We report an approach for the discovery of biomarkers that can predict tumour relapse and pathologic complete response (pCR) in TNBC on the basis of mRNA expression quantified using the NanoString nCounter Immunology Panel. To overcome the limited sample size, prediction models based on random Forest were constructed using the differentially expressed genes (DEGs) as selected features. We also evaluated the differences between pre- and post-treatment groups aiming for the combinatorial assessment of pCR and relapse using additive models in edgeR. RESULTS: We identify nine and 13 DEGs strongly associated with pCR and relapse, respectively, from 579 immune genes in a small number of samples (n = 55) using edgeR. An additive model for the comparison of pre- and post-treatment groups via the adjustment of the independent subject in the relapse group revealed associations for 41 genes. Comprehensive analysis indicated that our prediction models outperformed those constructed using features extracted from the existing feature selection model Elastic Net in terms of accuracy. The prediction models were assessed using a randomization test to validate the robustness (empirical P for the model of pCR = 0.015 and empirical P for the model of relapse = 0.018). Furthermore, three DEGs (FCER1A, EDNRB, and TGFBI) in the model of relapse showed prognostic significance for predicting the survival of patients with cancer through Cox proportional hazards regression model-based survival analysis. CONCLUSION: Gene expression quantified via the NanoString nCounter Immunology Panel can be seamlessly analysed using edgeR, even considering small sample sizes. Our approach provides a scalable framework that can easily be applied for the discovery of biomarkers based on the NanoString nCounter Immunology Panel. DATA AVAILABILITY: The source code will be available from github at https://github.com/sungheep/nanostring .

Hearing aids are still beneficial to patients, even if they have a low speech discrimination.

PURPOSE: A speech discrimination score (SDS) is a predictor for the successful use of hearing aids (HAs). This study is to evaluate the efficacy of HAs in patients with a low or poor SDS. METHODS: We enrolled 186 ears using HAs, with an unaided SDS ≤ 64%. They were categorized into four groups by their unaided SDS: 0-16% for Group 1, 20-32% for Group 2, 36-48% for Group 3, and 52-64% for Group 4. Aided SDS was measured 1, 3, 6, and 12 months after the use. The Hearing In Noise Test (HINT), the Hearing Handicap Inventory for the Elderly (HHIE), and the International Outcome Inventory for Hearing Aids (IOI-HA) were assessed. RESULTS: The SDS increased by 27.4% (12.0 to 39.4%) in Group 1, 26.4% (26.9 to 53.3%) in Group 2, 24.6% (42.2 to 66.8%) in Group 3, and 10.5% (59.5% to 70.0%) in Group 4. HINT composite scores significantly decreased from 22.5 to 15.1 in Group 1, 9.4 to 7.0 in Group 2, and 4.4 to 2.4 in Group 4. Total HHIE score changed from 48.2 to 24.2 in Group 1, 64.0 to 32.8 in Group 2, 37.1 to 16.6 in Group 3, and 55.8 to 40.1 in Group 4 (P < 0.05 in Groups 2, 3, and 4). CONCLUSION: In patients with a low SDS, a significant increase in SDS was achieved after the use of HAs, and subjective satisfaction was also acceptable. Low SDS might not be a contraindication for HAs.

Identification of Free-Living Amoebas in Tap Water of Buildings with Storage Tanks in Korea.

Free-living amoebas (FLAs) can cause severe disease in humans and animals when they become infected. However, there are no accurate survey reports on the prevalence of FLAs in Korea. In this study, we collected 163 tap water samples from buildings, apartments, and restrooms of highway service areas in 7 Korean provinces with high population density. All these buildings and facilities have water storage tanks in common. The survey was separated into categories of buildings, apartments, and highway service areas. Five hundred milliliters of tap water from each building was collected and filtered with 0.2 µm pore filter paper. The filters were incubated in agar plates with heated E. coli at 25°C. After axenization, genomic DNA was collected from each FLA, and species classification was performed using partial 18S-rDNA PCR-sequencing analysis. We found that 12.9% of tap water from buildings with storage tanks in Korea was contaminated with FLAs. The highway service areas had the highest contamination rate at 33.3%. All of the FLAs, except one, were genetically similar to Vermamoeba vermiformis (Hartmannella vermiformis). The remaining FLA (KFA21) was very similar to Acanthamoeba lugdunensis (KA/E26). Although cases of human infection by V. vermiformis are very rare, we must pay attention to the fact that one-third of tap water supplies in highway service areas have been contaminated.

Evaluation of onion juices quality following heat-treatment and their application as a sugar substitute in Kimchi.

This study was conducted to evaluate the quality of onion juices that had been heat-treated for different times as well as their use as a table sugar substitute in Kimchi. The onions were steamed at 100 ∘C for 30 min and boiled at 90 ∘C for 30, 60, and 120 min. The highest cycloalliin (0.76 mM), free-sugar (sucrose 1.66 g/L, glucose 8.62 g/L, and fructose 7.64 g/L), and malic acid (0.82 g/L) contents were observed in onion boiled at 90 ∘C for 120 min. The possibility of using heat-treated onion juices as an alternative to table sugar in Kimchi was evaluated by comparing the lactic acid bacteria count, pH, acidity, organic acid, and free-sugar in these juices with those in Kimchi prepared using table sugar (control). The total viable bacteria and lactic acid bacteria showed similar growth patterns as in the control. The average pH reduction and increase in titratable acidity (%) in all treated Kimchi samples during fermentation for 4 weeks were 1.18 ± 0.05 and 0.81 ± 0.06, respectively. Kimchi with onion juice heat-treated for 120 min (K120) had the most similar lactic acid and acetic acid contents to that in the control after fermentation for 4 weeks. The highest mannitol level after fermentation for 4 weeks was detected in K120, which showed better sensory qualities compared to the control.

Efficacy of Virtual Reality Combined With Real Instrument Training for Patients With Stroke: A Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy of real instrument training in virtual reality (VR) environment for improving upper-extremity and cognitive function after stroke. DESIGN: Single-blind, randomized trial. SETTING: Medical center. PARTICIPANTS: Enrolled subjects (N=31) were first-episode stroke, assessed for a period of 6 months after stroke onset; age between 20 and 85 years; patients with unilateral paralysis and a Fugl-Meyer assessment upper-extremity scale score >18. INTERVENTIONS: Both groups were trained 30 minutes per day, 3 days a week, for 6 weeks, with the experimental group performing the VR combined real instrument training and the control group performing conventional occupational therapy. MAIN OUTCOME MEASURES: Manual Muscle Test, modified Ashworth scale, Fugl-Meyer upper motor scale, hand grip, Box and Block, 9-Hole Peg Test (9-HPT), Korean Mini-Mental State Examination, and Korean-Montreal Cognitive Assessment. RESULTS: The experimental group showed greater therapeutic effects in a time-dependent manner than the control group, especially on the motor power of wrist extension, spasticity of elbow flexion and wrist extension, and Box and Block Tests. Patients in the experimental group, but not the control group, also showed significant improvements on the lateral, palmar, and tip pinch power, Box and Block, and 9-HPTs from before to immediately after training. Significantly greater improvements in the tip pinch power immediately after training and spasticity of elbow flexion 4 weeks after training completion were noted in the experimental group. CONCLUSIONS: VR combined real instrument training was effective at promoting recovery of patients' upper-extremity and cognitive function, and thus may be an innovative translational neurorehabilitation strategy after stroke.

Kimchi extracts as inhibitors of colour deterioration and lipid oxidation in raw ground pork meat during refrigerated storage.

BACKGROUND: Kimchi is a Korean, traditional fermented food made from Korean cabbage, radish, fermented jeotgal, ginger, garlic, and red pepper powder. It is a good source of natural antioxidants such as phenolic compounds, flavonoids, vitamins, and carotenoids. In this study, the antioxidant effects of various kimchi extracts on raw ground pork during refrigerated storage were investigated. Raw ground pork samples were treated with ascorbic acid, butylated hydroxyl toluene, baechu kimchi extract (BKE), gat kimchi extract (GKE), puchu kimchi extract (PKE), and white kimchi extract (WKE) and compared with raw ground pork without antioxidant treatment (NC). RESULTS: Increased metmyoglobin (MetMb), thiobarbituric acid reacting substance (TBARS), and total bacterial counts (TBC) were observed in all meat samples after storage, whereas pH, lightness, and redness values tended to decrease with increased storage time. All treated samples had lower TBARS and MetMb values and TBC compared to the control samples. Various kimchi ethanol extracts protected raw ground pork from lipid oxidation. The most potent antioxidant was GKE, whereas WKE was the weakest. CONCLUSIONS: This study suggests that the tested extracts, especially kimchi, have potential as natural preservatives to reduce colour degradation, lipid oxidation, and bacterial count in raw ground pork meat. © 2018 Society of Chemical Industry.

Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.

In eukaryotes, cyclin-dependent kinases (CDKs) control the cell cycle and critical steps in gene expression. The lethal parasite Trypanosoma brucei, member of the phylogenetic order Kinetoplastida, possesses eleven CDKs which, due to high sequence divergence, were generically termed CDC2-related kinases (CRKs). While several CRKs have been implied in the cell cycle, CRK9 was the first trypanosome CDK shown to control the unusual mode of gene expression found in kinetoplastids. In these organisms, protein-coding genes are arranged in tandem arrays which are transcribed polycistronically. Individual mRNAs are processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. CRK9 ablation was lethal in cultured trypanosomes, causing a block of trans splicing before the first transesterification step. Additionally, CRK9 silencing led to dephosphorylation of RNA polymerase II and to hypomethylation of the SL cap structure. Here, we tandem affinity-purified CRK9 and, among potential CRK9 substrates and modifying enzymes, discovered an unusual tripartite complex comprising CRK9, a new L-type cyclin (CYC12) and a protein, termed CRK9-associated protein (CRK9AP), that is only conserved among kinetoplastids. Silencing of either CYC12 or CRK9AP reproduced the effects of depleting CRK9, identifying these proteins as functional partners of CRK9 in vivo. While mammalian cyclin L binds to CDK11, the CRK9 complex deviates substantially from that of CDK11, requiring CRK9AP for efficient CRK9 complex formation and autophosphorylation in vitro. Interference with this unusual CDK rescued mice from lethal trypanosome infections, validating CRK9 as a potential chemotherapeutic target.

Comparison and Combination of Strain and Shear Wave Elastography of Breast Masses for Differentiation of Benign and Malignant Lesions by Quantitative Assessment: Preliminary Study.

OBJECTIVES: To compare the diagnostic performance of strain and shear wave elastography of breast masses for quantitative assessment in differentiating benign and malignant lesions and to evaluate the diagnostic accuracy of combined strain and shear wave elastography. METHODS: Between January and February 2016, 37 women with 45 breast masses underwent both strain and shear wave ultrasound (US) elastographic examinations. The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) final assessment on B-mode US imaging was assessed. We calculated strain ratios for strain elastography and the mean elasticity value and elasticity ratio of the lesion to fat for shear wave elastography. Diagnostic performances were compared by using the area under the receiver operating characteristic curve (AUC). RESULTS: The 37 women had a mean age of 47.4 years (range, 20-79 years). Of the 45 lesions, 20 were malignant, and 25 were benign. The AUCs for elasticity values on strain and shear wave elastography showed no significant differences (strain ratio, 0.929; mean elasticity, 0.898; and elasticity ratio, 0.868; P > .05). After selectively downgrading BI-RADS category 4a lesions based on strain and shear wave elastographic cutoffs, the AUCs for the combined sets of B-mode US and elastography were improved (B-mode + strain, 0.940; B-mode + shear wave; 0.964; and B-mode, 0.724; P < .001). Combined strain and shear wave elastography showed significantly higher diagnostic accuracy than each individual elastographic modality (P = .031). CONCLUSIONS: These preliminary results showed that strain and shear wave elastography had similar diagnostic performance. The addition of strain and shear wave elastography to B-mode US improved diagnostic performance. The combination of strain and shear wave elastography results in a higher diagnostic yield than each individual elastographic modality.

Factors influencing the outcome from ultrasonography-guided fine-needle aspiration of benign thyroid cysts and partially cystic thyroid nodules: A multicenter study.

PURPOSE: The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FNA of the cystic component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and to evaluate the factors influencing the outcome. METHODS: From June to December 2013, seven radiologists at seven institutions prospectively performed US-FNA on 320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least one follow-up US examination following US-FNA of the cystic component at each institution by the same radiologist. A variety of factors, including US features of cystic thyroid nodules, the characteristics of the aspirates, and the follow-up US findings, were analyzed. RESULTS: Of 179 cystic thyroid nodules, there were 53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies were detected. On follow-up US, the mean size reduction rate of the cystic component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to the response group. On univariate analysis, the degree of aspiration and time interval between US-FNA and the final follow-up US showed the significant differences between the response and no response groups. On multivariate analysis, the only factor that influenced the outcome was the nodule type. The cystic component's positive response rate after simple aspiration was higher in the thyroid cysts than in the PCTNs. CONCLUSIONS: US-FNA may be effective at collapsing the cystic components of benign thyroid cysts and PCTNs.

Distinguishing benign from malignant thyroid nodules using thyroid ultrasonography: utility of adding superb microvascular imaging and elastography.

OBJECTIVE: Thyroid nodules are common; however, malignancy is less than 7%. Therefore, additional techniques such as Doppler ultrasonography or elastography are used to improve diagnostic performance of conventional ultrasonography. We want to prospectively investigate the use of additional superb microvascular imaging (SMI) and strain elastography to B-mode ultrasound in thyroid nodules in distinguishing benign from malignant thyroid nodules. METHODS: We analyzed 52 thyroid nodules (malignant = 26, benign = 26) and reviewers scored the likelihood of malignancy for three data sets (i.e., B-mode ultrasonography alone, B-mode ultrasonography + SMI, and B-mode ultrasonography + strain elastography). The area under the receiver-operating characteristic curve (Az) values, sensitivities, and specificities were compared. RESULTS: A comparison of the data sets revealed that area under the receiver-operating characteristic curve values were similar without statistical difference. However, on comparing sensitivity and specificity based on the management decision of whether to conduct fine-needle aspiration (FNA) after combining information from all three types of imaging (B-mode ultrasonography + SMI + strain elastography), specificity was significantly higher for the combined technique (34.6%) than for B-mode ultrasonography alone (11.5%), without decrease in sensitivity (P = 0.032). CONCLUSION: Additional use of SMI and strain elastography could potentially lead to increase in specificity in thyroid ultrasonography.

LAPS Insulin115: A novel ultra-long-acting basal insulin with a unique action profile.

AIMS: To conduct a comprehensive pre-clinical study of the novel ultra-long acting insulin analogue LAPS Insulin115. METHODS: Pharmacokinetic/pharmacodynamic studies comparing LAPS Insulin115 with other basal insulins were conducted in genetically diabetic (db/db) mice. Insulin signalling in the major target organs was analysed using Western blot after single subcutaneous injection in wild-type male Wistar rats. Using in vitro assays we analysed transendothelial transport, insulin receptor (IR) interaction, and the mitogenic and metabolic properties of LAPS Insulin115. Furthermore, IR downregulation after long-term exposure to high concentrations of LAPS Insulin115 was analysed using an in vitro desensitization/resensitization model. RESULTS: The novel Fc-conjugated insulin derivative LAPS Insulin115 showed an extensively prolonged pharmacokinetic and pharmacodynamic profile in rodents. Despite its size of 59 kDa, LAPS Insulin115 passes the vascular endothelial barrier and induces insulin signalling in all major target tissues in rats. In vitro, LAPS Insulin115 showed a very slow onset of action because of its reduced IR affinity; however, after long-term stimulation it was equipotent in respect to its metabolic potency and showed no increased mitogenic action when compared with regular insulin. Remarkably, under conditions of chronic exposure, LAPS Insulin115 does not induce irreversible desensitization of target cells, which is probably attributable to much less prominent IR downregulation. CONCLUSION: Thus, LAPS Insulin115 exhibits a unique in vivo and in vitro profile and thereby represents an excellent candidate for a once-weekly insulin analogue.

The role of NdgR in glycerol metabolism in Streptomyces coelicolor.

Streptomyces, which produces many pharmaceutical antibiotics and anticancer agents, is a genus of soil-dwelling bacteria with numerous regulators that control both primary and secondary metabolism. NdgR is highly conserved in Streptomyces spp. and is known to be involved in antibiotic production, tolerance against shock and physical stress, nitrogen metabolism, leucine metabolism, and N-acetylglucosamine metabolism. As another function of NdgR, we report the involvement of NdgR in glycerol metabolism in S. coelicolor. Initially, a glycerol utilization operon containing gylCABX was found to be up-regulated in an ndgR deletion mutant (BG11) grown in N-acetylglucosamine solid minimal media compared with wild-type strain (M145). BG11 produced more antibiotics with a small amount of glycerol and increased glycerol utilization, yielding higher concentrations of lactate and acetate per cell. Moreover, fatty acid production was also changed in BG11 to produce longer chain fatty acids, phenolic compounds, alkanes, and fatty alcohols. Using a gel retardation assay, NdgR was found to bind the upstream region of gylC, working as a repressor. NdgR is a second regulator of a glycerol utilization operon, for which only one regulator, GylR was previously known.

ChARM: Discovery of combinatorial chromatin modification patterns in hepatitis B virus X-transformed mouse liver cancer using association rule mining.

BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells. RESULTS: We report a new computational approach, ChARM (Combinatorial Chromatin Modification Patterns using Association Rule Mining), that can be employed for the discovery of de novo combinatorial patterns of differential chromatin modifications. We used ChARM to analyse chromatin modification data from the livers of normal (non-cancerous) mice and hepatitis B virus X (HBx)-transgenic mice with hepatocellular carcinoma, and discovered 2,409 association rules representing combinatorial chromatin modification patterns. Among these, the combination of three histone modifications, a loss of H3K4Me3 and gains of H3K27Me3 and H3K36Me3, was the most striking pattern associated with the cancer. This pattern was enriched in functional elements of the mouse genome such as promoters, coding exons and 5'UTR with high CpG content, and CpG islands. It also showed strong correlations with polymerase activity at promoters and DNA methylation levels at gene bodies. We found that 30 % of the genes associated with the pattern were differentially expressed in the HBx compared to the normal, and 78.9 % of these genes were down-regulated. The significant canonical pathways (Wnt/ß-catenin, cAMP, Ras, and Notch signalling) that were enriched in the pattern could account for the pathogenesis of HBx. CONCLUSIONS: ChARM, an unsupervised method for discovering combinatorial chromatin modification patterns, can identify histone modifications that occur globally. ChARM provides a scalable framework that can easily be applied to find various levels of combination patterns, which should reflect a range of globally common to locally rare chromatin modifications.