Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). ...Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.
MicroRNAs in exosomes (exosomal miRNAs) have attracted increased attention as cancer biomarkers for early diagnosis and prognosis owing to their stability in body fluids. Since strong association ...exists between exosomal miRNA expression levels and breast cancer, the development of effective methods that can monitor exosomal miRNA expression both over broad concentration ranges and in ultralow amounts is critical. Here, a surface‐enhanced Raman scattering (SERS)‐based sensing platform is developed for the quantitative determination of exosomal miRNAs. Ultrasensitive exosomal miRNA detection with single‐nucleotide specificity is obtained from enhanced SERS signals from a uniform plasmonic head‐flocked gold nanopillar substrate, which generates multiple hotspots and enables hybridization between short oligonucleotides, i.e., miRNAs and locked nucleic acid probes. The proposed SERS sensor shows an extremely low detection limit without any amplification process, a wide dynamic range (1 am to 100 nm), multiplex sensing capability and sound miRNA recovery in serum. Furthermore, this sensor allows reliable observation of exosomal miRNA expression patterns from breast cancer cell lines and can discriminate breast cancer subtype based on the difference between these patterns. The results suggest that this sensor can be used for universal cancer diagnosis and further biomedical applications through the quantitative measurement of exosomal miRNAs in bodily fluids.
A surface‐enhanced Raman scattering (SERS)‐based sensing platform for quantitative determination of exoxosmal miRNA is developed for quantitative determination of exosomal miRNAs. Ultrasensitivity and high specificity of miRNA detection are provided by the collection of enhanced SERS signals from uniform plasmonic head‐flocked gold nanopillar SERS substrates, which create self‐assembled hot spots and enabled hybridization between locked nucleic acid probes and miRNAs.
Objective
To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image‐based tau staging in the Alzheimer disease (AD) spectrum.
...Methods
We included 195 participants (53 AD, 52 amnestic mild cognitive impairment MCI, 23 nonamnestic MCI, and 67 healthy controls) who underwent 2 PET scans (18F‐florbetaben for amyloid‐β and 18F‐AV‐1451 for tau). We assumed that regions with earlier appearances of pathology may show increased binding in a greater number of participants and acquired spreading order of tau accumulation by sorting the regional frequencies of involvement. We classified each participant into image‐based tau stage based on the Z score of the composite region for each stage.
Results
Tau accumulation was most frequently observed in the medial temporal regions and spread stepwise to the basal and lateral temporal, inferior parietal, posterior cingulate, and other association cortices, and then ultimately to the primary cortical regions. In contrast, amyloid accumulation was found with similar frequency in the diffuse neocortical areas and then finally spread to the medial temporal regions. The image‐based tau stage correlated with the general cognitive status, whereas cortical thinning was found only in the advanced tau stages: medial temporal region in stage V and widespread cortex in stage VI.
Interpretation
Our PET study replicated postmortem spreading patterns of tau and amyloid‐β pathologies. Unlike the diffuse accumulation of amyloid throughout the neocortex, tau spreading occurred in a stepwise fashion through the networks. Image‐based tau staging may be useful for the objective assessment of AD progression. Ann Neurol 2016;80:247–258
Low serum bilirubin levels have been associated with increased risk of cardiovascular disease (CVD) and metabolic syndrome. Testosterone deficiency could also contribute to increased risk of CVD and ...metabolic syndrome. Therefore, this study aimed to examine the relationship between serum bilirubin level and testosterone deficiency in 1284 Korean men aged 45 to 70 years. Serum bilirubin level was categorized into quartiles: Q1 ≤ 0.7, Q2 0.8-0.9, Q3 1.0-1.1, and Q4 ≥ 1.2 mg/dL. Testosterone deficiency was defined as level less than 8.0 nmol/L, as suggested by the position statement of International Society of Andrology. The overall prevalence of testosterone deficiency was 5.8% and significantly decreased with the quartiles from Q1 to Q4. Compared with the referent fourth quartile (serum bilirubin ≥ 1.2 mg/dL), the ORs (95% CIs) for testosterone deficiency was 2.29 (1.04-4.94) for the first quartile after adjusting for age, fasting glucose, triglyceride, HDL-cholesterol, leukocyte count, hemoglobin, smoking status, and alcohol intake. We found inversely graded associations of serum bilirubin level with testosterone deficiency. These findings suggest that low bilirubin level may be interpreted as a state of testosterone deficiency in middle-aged and older men.
•The TyG index predicts type 2 diabetes (T2D) prevalence better than HOMA-IR.•The TyG index showed superior predictability for incidence of T2D than HOMA-IR.•The optimal value of the TyG index and ...HOMA-IR predicting T2D are low in East Asians.
Insulin resistance is an independent risk factor for developing type 2 diabetes. Therefore, this study compared the predictability of the triglyceride–glucose (TyG) index and the homeostatic model assessment of insulin resistance (HOMA-IR) for the prevalence and incidence of type 2 diabetes.
We analyzed data from 9730 adults aged 40–69 years at baseline and 7783 participants without diabetes who were followed up in the Korean Genome and Epidemiology Study survey. From 2001 to 2002 (baseline survey) to 2013–2014, this survey was conducted biennially (six follow-ups). The average follow-up period was 9.0 years.
The TyG index showed better predictability for the prevalence of type 2 diabetes than HOMA-IR (TyG index: 0.784, HOMA-IR: 0.728, p < 0.001). The area under the time-dependent receiver operating characteristic curve of the TyG index for incident type 2 diabetes was 0.640 (0.628–0.652), which was significantly higher than that of HOMA-IR 0.531 (0.521–0.541) (p < 0.001).
The TyG index is superior to HOMA-IR for predicting type 2 diabetes. The TyG index could, therefore, be more useful for the early detection and prevention of type 2 diabetes.
The use of statins in nonalcoholic fatty liver disease (NAFLD) may reduce cardiovascular morbidity, although their effect on NAFLD itself is not well known. We aimed to investigate the role of ...statins on the development of de novo NAFLD and progression of significant liver fibrosis.
This study included 11,593,409 subjects from the National Health Information Database of the Republic of Korea entered in 2010 and followed up until 2016. NAFLD was diagnosed by calculating fatty liver index (FLI), and significant liver fibrosis was evaluated using the BARD score. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection.
Among 5,339,901 subjects that had a FLI < 30 and included in the non-NAFLD cohort, 164,856 subjects eventually had NAFLD developed. The use of statin was associated with a reduced risk of NAFLD development (adjusted odds ratio AOR 0.66; 95% confidence interval CI 0.65-0.67) and was independent of associated diabetes mellitus (DM) (with DM: AOR 0.44; 95% CI 0.41-0.46, without DM: AOR 0.71; 95% CI 0.69-0.72). From 712,262 subjects with a FLI > 60 and selected in the NAFLD cohort, 111,257 subjects showed a BARD score ≥ 2 and were defined as liver fibrosis cases. The use of statins reduced the risk of significant liver fibrosis (AOR 0.43; 95% CI 0.42-0.44), independent of DM (with DM: AOR 0.31; 95% CI 0.31-0.32, without DM: AOR 0.52; 95% CI 0.51-0.52).
In this large population-based study, statin use decreased the risk of NAFLD occurrence and the risk of liver fibrosis once NAFLD developed.
Objectives
To evaluate the effect of training radiology residents on breast ultrasonography (US) according to the Breast Imaging Reporting And Data System (BI-RADS) and the factors that influence the ...training effect.
Methods
This multicenter, prospective study was approved by eight institutional review boards. From September 2013 to July 2014, 248 breast masses in 227 women were included for US image acquisition. Representative B-mode and video images of the breast masses were recorded, among which 54 cases were included in the education set and 66 in the test set. Sixty-one radiology residents scheduled for breast imaging training individually reviewed the test set, immediately before, 1 month after, and 6 months after training. Diagnostic performances and US descriptors of the residents were evaluated and compared against those of expert radiologists.
Results
Agreements between residents and experienced radiologists showed improvement after training, while agreements between post-training and post-6-month training descriptors did not show significant differences (all
p
> 0.05, respectively). Sensitivity, negative predictive value (NPV), and AUC were significantly improved for residents post-training and post-6-month training (all
p
< 0.05), while approximating the performances of expert radiologists except for AUC (0.836, 0.840, and 0.908, respectively,
p
< 0.05). Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC.
Conclusion
Training using education material dedicated for breast US imaging effectively improved the diagnostic performances of radiology residents and agreements with experienced radiologists on US BI-RADS features.
Key Points
• Agreements on lesion descriptors between residents and experienced radiologists showed improvement after training, regardless of test point.
• Sensitivity, NPV, and AUC were significantly improved for residents in post-training and post-6-month training (all p < 0.05).
• Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC.
Background
Postoperative throat complications after intubation are undesirable but frequent outcomes. A randomized, double‐blinded study was performed to determine whether thermal softening of ...endotracheal tubes reduced throat complications after intubation.
Methods
Patients (n = 196) undergoing nasal surgery were randomly allocated into the control group and thermal softening groups. Sore throat and hoarseness were evaluated 1 and 24 hours after extubation. The severity of sore throat was evaluated using the numeric rating scale (NRS). The primary outcome was the incidence of sore throat 1 hour after extubation and sore throat was defined as a painful or scratchy feeling in the throat. The secondary outcomes were the incidence of hoarseness 1 hour after extubation, the incidence of sore throat and hoarseness 24 hours after extubation, severity of sore throat, and vocal cord injuries.
Results
The incidence of sore throat 1 hour after extubation was lower in the thermal softening group than in the control group (35.1% vs 52.7%, P = .02). Moreover, thermal softening decreased the mean NRS score for sore throat in the thermal softening group by 10% an hour after extubation (thermal softening group, 1.29 95% CI, 0.88‐1.70 vs control group, 2.33 95% CI, 1.77‐2.89; P < .01). At 24 hours after extubation, the incidence of sore throat (38.3% vs 40.7%, P = .77) and hoarseness (34.0% vs 35.2%, 0.95 0.52‐1.74, P = .74) were comparable between the two groups.
Conclusions
Intubation using endotracheal tubes with thermal softening significantly decreased the incidence of sore throat 1 hour after extubation when compared with endotracheal tubes without thermal softening.
Objective
Periodontitis and osteoarthritis are major public health concerns that result in decreased quality of life among middle‐aged and older adults. We sought to examine whether the severity of ...periodontitis is related to osteoarthritis according to the presence of type 2 diabetes mellitus.
Methods
This study included 3,527 participants age ≥50 years from the Korean National Health and Nutrition Examination Survey. Periodontitis was assessed using the Community Periodontal Index; severe periodontitis was defined as periodontal tissue forming deep periodontal pockets ≥6‐mm depth. Osteoarthritis was defined as Kellgren/Lawrence grade ≥2 on radiographic images of the knee or hip area with joint pain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for osteoarthritis according to the severity of periodontitis, stratified by type 2 diabetes mellitus, were calculated using multiple logistic regression analyses.
Results
Participants with type 2 diabetes mellitus were more likely to have osteoarthritis as the severity of periodontitis increased (nonsevere periodontitis OR 1.23 95% CI 0.67–2.32; severe periodontitis OR 3.01 95% CI 1.51–5.84) after adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, education level, household income, hypertension, and frequent tooth‐brushing. However, this positive association was not found in individuals without type 2 diabetes mellitus after adjusting for the same covariables.
Conclusion
Severe periodontitis was positively and significantly associated with osteoarthritis in middle‐aged and older individuals with type 2 diabetes mellitus. Our findings suggest that the oral inflammation manifesting in periodontitis may be at least partly involved in the pathogenesis of osteoarthritis, particularly in patients with type 2 diabetes mellitus.
The present retrospective study reviewed the association among sarcopenia, myosteatosis, and overall survival (OS) in patients with postoperative colorectal cancer (CRC) with regard to age.
A ...retrospective study was conducted with a five-year follow-up.
Data from all patients with CRC, who underwent surgery between February 2005 and April 2014, were reviewed.
Data from 1053 patients (622 male 59.1%, 431 female 40.9%; mean ± SD age, 62.8 ± 11.8 years) were analyzed.
Patients were divided into three groups according to age: ≤50, 51–74, and ≥75 years. Data, including perioperative parameters, and the presence of sarcopenia and myosteatosis according to skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), respectively, were collected. Sarcopenia was evaluated using CT by calculating the SMI at the L3 level by dividing the area of the skeletal muscle by height squared (cm2/m2). SMD was also calculated using CT at the L3 level, but by evaluating fat attenuation according to Hounsfield units (HU).
Patient allocation according to age group was as follows: ≤50 years, n = 147 (14.0%); 51–74 years, n = 742 (70.5%); and ≥75 years, n = 164 (15.5%). The presence of sarcopenia and myosteatosis were statistically significant with increasing age (P = 0.004 and P < 0.001, respectively). The 51–74 years age group exhibited a significant association in OS for myosteatosis (P < 0.001) while the ≥75 years group was significantly associated with sarcopenia (P = 0.04) with regard to OS. Multivariable analysis also revealed a statistically significant association between myosteatosis in the 51–74 years age group (P = 0.033) and sarcopenia in the ≥75 years age group (P = 0.005) even when adjusted for recurrence status.
Different age groups exhibited significantly variable skeletal muscle indices. Although an abundance of irrefutable results demonstrated a correlation between CT-defined sarcopenia, myosteatosis, and clinical prognosis, data regarding age-dependent correlations are scarce. Results of this study demonstrated that sarcopenia and myosteatosis did not influence the prognosis of young patients with postoperative CRC (≤50 years of age), inferring the existence of significantly different skeletal muscle-related parameters according to age. Patients over 75 years of age showed significant association with sarcopenia while those in the 51–74 age group displayed significant link to myosteatosis. Clinicians should consider the impact of sarcopenia and myosteatosis on patient prognosis and should also be aware that the effect may differ according to patient age.
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