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Abstract Background Hypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post‐AFCA reverse remodeling and AF recurrence based on HCM presence and subtype. Methods Among 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age‐, gender‐, and AF type‐matched. Between AF‐HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1‐year follow‐up, and procedural outcomes over the course of follow‐up between two groups. Results A total of 122 AF‐HCM patients and 318 control patients were included. AF‐HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p

Abstract Background Metabolic syndrome is associated with type 2 diabetes and its prevalence is increasing worldwide in young adults. We aimed to determine whether cumulative exposure to metabolic syndrome is associated with type 2 diabetes risk in young adults. Methods Data of 1,376,540 participants aged 20–39 years without a history of type 2 diabetes and who underwent four annual health check-ups were collected. In this large-scale prospective cohort study, we evaluated the incidence rates and hazard ratios (HRs) of diabetes according to cumulative frequencies of metabolic syndrome over 4 years of consecutive annual health check-ups (burden score 0–4). Subgroup analyses were performed by sex and age. Results During 5.18 years of follow-up, 18,155 young adults developed type 2 diabetes. The incidence of type 2 diabetes increased with burden score (P

Abstract Background Phosphodiesterase type 5 inhibitors restore nitric oxide signaling, that plays a significant role in erectile function, and appears to counteract insulin resistance in animal and human models. This study was aimed to evaluate the glycemic and metabolic effects of low-dose tadalafil once daily in patients with type 2 diabetes and erectile dysfunction. Methods A 6-month, randomized, double-blind, placebo-controlled pilot trial was conducted. Eligible patients were randomly assigned in a ratio of 2:1 to the tadalafil 5 mg and placebo groups; all patients received either tadalafil or placebo once a day. The primary efficacy endpoint was the absolute change in glycated hemoglobin (HbA1c) levels during the 6-month study period. The secondary efficacy endpoints included metabolic parameters and erectile function. Results Of the 68 patients who completed this study, 45 and 23 patients were allocated to the tadalafil and placebo groups, respectively. The mean HbA1c level was significantly different between the groups over the 6-month study period (P = 0.021). After 6 months of treatment, the HbA1c decrement in the tadalafil group was greater than that in the placebo group (− 0.14 ± 0.53% vs. 0.20 ± 0.69%, P = 0.030). The International Index of Erectile Function-5 scores improvement was significantly greater in the tadalafil group than in the placebo group at 6 months (P = 0.003). Conclusion This prospective pilot study showed that low-dose tadalafil administered once a day was effective in improving glycemic control and erectile function in patients with type 2 diabetes and erectile dysfunction. Trial registration KCT0005666

Abstract Background An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. Methods MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. Results Of the 85 patients [age, 54.0 (41.0–65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65–148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02–1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08–1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. Conclusions The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Although left atrial (LA) dimension (LAD) is one of the predictors of atrial fibrillation (AF) recurrence after catheter ablation, repetitive recurrences occur in patients without enlarged LAD. We explored the predictive value of pulmonary vein (PV) to LA volume percent ratio (PV/LA%vol) for rhythm outcomes after AF catheter ablation (AFCA). We included 2913 patients (73.5% male, 60.0 [52.0–67.0] years old, 60.6% paroxysmal AF) who underwent AFCA. We evaluated the association between PV/LA%vol and AF recurrence after AFCA and compared the predictive value for AF recurrences according to the LA size with LAD. We additionally investigated the association between PV/LA%vol and PITX2 gene using a genome-wide association study. LAD affected 1-year recurrence only in the highest tertile group (T3, p = 0.046), but PV/LA%vol determined 1-year recurrence in all LAD groups (T1, p = 0.044; T2, p = 0.021; and T3, p = 0.045). During 20.0 (8.0–45.0) months of follow-up, AF recurrence rate was significantly higher in patients with lower PV/LA%vol (Log-rank p = 0.004, HR 0.91 [0.84–1.00], p = 0.044). In the T1 and T2 LAD groups, predicting AF recurrences was better with PV/LA%vol than with LAD (AUC 0.63 vs. 0.51, p < 0.001 at T1; AUC 0.61 vs. 0.50, p = 0.007 at T2). We replicated PITX2-related rs12646447, which was independently associated with PV/LA%vol (β = 0.15 [0–0.30], p = 0.047). In conclusion, smaller PV volumes after LA volume adjustments have genetic background of PITX2 gene and predictive value for poorer rhythm outcomes after AFCA, especially in patients without LA enlargement.

Abstract Backgrounds Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD). Methods Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients. Results The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P

Vitiation air heater (VAH) combustion characteristics for a direct-connect scramjet combustor (DCSC) were experimentally studied. The VAH consists of a head, modular chamber, and circular-to-rectangular shape transition (CRST) nozzle. The CRST nozzle transforms the circular cross-sectioned rocket-type VAH into a rectangular cross-sectioned scramjet combustor. The CRST nozzle exit Mach numbers at the top, middle, and bottom were measured using a tungsten wedge. The oblique shock formed by the wedge was captured using Schlieren visualization and recorded with a high-speed camera. The θ-β-M relation showed that the exit Mach number was 2.04 ± 0.04 with a chamber pressure of 1.685 ± 0.07 MPa. With the VAH design point verified, preliminary scramjet combustor ignition tests were conducted. As the fuel was not auto-ignited by the vitiated air, the forced ignition method, in which VAH ignition flame ignites the scramjet fuel, was used. The Schlieren images showed that a cavity shear layer combustion mode was formed and also showed that the forced ignition method could be used as a reference model for the ignitor-ignition method.

This study focuses on revisiting the tectostratigraphic framework of the Ulleung Basin and conceptualizing neotectonics around the western East Sea margin. Based on the analysis of 2D and 3D multi-channel seismic reflection data and offshore drill wells, we divided the entire sedimentary successions of the Ulleung Basin into four tectostratigraphic sequences, named TS1 (c. 23–16 Ma), TS2 (c. 16–9 Ma), TS3 (c. 9–4 Ma), and TS4 (c. 4 Ma–present), in ascending order. The results show that each sequence has been deformed once or multiple times in different periods by juxtaposing two major compressional structures named the Dolgorae Thrust-Fold Belt and the Gorae Anticline. Interpretation of the stratal deformation and termination patterns of the syn- and post-deformational sequences of each structures suggests that the thrusting and folding of the Dolgorae Thrust-Fold Belt was active from c. 16 Ma to c. 9 Ma under the NNW–SSE compressional stress regime (Stage-2), whereas the Gorae Anticline was active from 4 Ma to the present under the ENE–WSW compressional stress regime (Stage-4). Between these two compressional events, there was an intervening period of regional slow subsidence driven by thermal contraction of the back-arc lithosphere and isostatic sedimentary loading (Stage-3). Based on the stratigraphic and structural reconstruction, we propose a 4-stage tectonic model: Stage-1) back-arc opening stage associated with the southward drift of the Japanese islands (c. 23–16 Ma), Stage-2) tectonic-inversion stage in association with the reorganization of the Pacific and Philippine Sea plates and clockwise rotation of SW Japan (c. 16–9 Ma), Stage-3) post-inversion stage with regional thermal and isostatic subsidence (c. 9–4 Ma), and Stage-4) neotectonic stage in which embryonic subduction is nucleating on the East Sea margins under the E–W compressional stress regime (c. 4 Ma–present).

A noncircular engine cross-section could provide great flexibility in the integration of propulsion into the airframe. In this work, a tri-arc RDE was constructed and tested as an example of noncircular cross-sectioned RDE. The operational characteristics of detonation wave propagation and thrust performance were investigated and compared with an equivalent circular RDE under the same operating conditions. High-speed camera images, short-time Fourier transform (STFT), and fast Fourier transform (FFT) were used for the investigation. The tri-arc RDE showed very similar characteristics to the circular RDE but exhibited slightly better stability and propulsion performance than the circular RDE. We consider that repeated curvature changes positively affect the stability of detonation wave propagation. The experimental data show contradicting results from the numerical analysis with a homogeneous mixture assumption in which the detonation pressures at the convex corner were greater than those at the concave corner. It is reasoned that the tri-arc injector design provides a non-uniform mixture composition, resulting in a strong detonation at the convex corner. Overall, the noncircular RDE of a tri-arc shaped cross-section is demonstrated, one which performs slightly better than an ordinary circular-shaped RDE both in detonation stability and performance.

Catheter ablation is the most effective rhythm control method for patients with atrial fibrillation (AF); however, it inevitably causes atrial tissue damage. We previously reported that AF catheter ablation (AFCA) increases left atrial (LA) pressure without changes in symptom scores. We hypothesized that extensive LA ablation increased the risk of stiff LA physiology. We included 1,720 patients (69.1% male, 60.0 [53.0–68.0] years old, 66.2% with paroxysmal AF) who underwent de novo AFCA and echocardiography before and 1-year after the procedure. Stiff LA physiology was defined, when the amount of the estimated pulmonary arterial pressure increase between the pre-procedural and the 1-year post-procedural follow-up echocardiography was >10 mmHg and when right ventricular systolic pressure (RVSP) was >35 mmHg at 1-year follow-up echocardiography. The failed rhythm control within 1 year was defined as recurrent AF despite using anti-arrhythmic drugs or cardioversion within a year of AFCA. We explored the incidence and risk factors for stiff LA physiology and the rhythm outcome of AFCA. Among the 1,720 patients, 64 (3.7%) had stiff LA physiology 1 year after AFCA. Stiff LA physiology was independently associated with diabetes (odds ratio [OR], 2.36 [95% CI, 1.14–4.87], p = 0.020), the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em; OR, 1.04 [95% CI, 1.00–1.10], p = 0.049), LA pulse pressure (Model 2: OR, 1.05 [95% CI, 1.00–1.11], p = 0.049), low LA voltage (OR, 0.36 [95% CI, 0.18–0.74], p = 0.005), empirical extra-pulmonary vein (PV) LA ablation (OR, 2.60 [95% CI, 1.17–5.74], p = 0.018), and radiofrequency (RF) ablation duration (Model 2: OR, 1.02 [95% CI, 1.01–1.03], p = 0.003). Although the incidence of post-AFCA stiff LA physiology was 3.7% and most of the cases were subclinical, the empirical extra-PV ablation was associated with this undesirable condition. In addition, patients who had low mean LA voltage before AFCA could be susceptible to stiff LA physiology.

Atrial stretch may contribute to the mechanism of atrial fibrillation (AF) recurrence after atrial fibrillation catheter ablation (AFCA). We tested whether the left atrial (LA) wall stress (LAW-stress[measured]) could be predicted by artificial intelligence (AI) using non-invasive parameters (LAW-stress[AI]) and whether rhythm outcome after AFCA could be predicted by LAW-stress[AI] in an independent cohort. Cohort 1 included 2223 patients, and cohort 2 included 658 patients who underwent AFCA. LAW-stress[measured] was calculated using the Law of Laplace using LA diameter by echocardiography, peak LA pressure measured during procedure, and LA wall thickness measured by customized software (AMBER) using computed tomography. The highest quartile (Q4) LAW-stress[measured] was predicted and validated by AI using non-invasive clinical parameters, including non-paroxysmal type of AF, age, presence of hypertension, diabetes, vascular disease, and heart failure, left ventricular ejection fraction, and the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em). We tested the AF/atrial tachycardia recurrence 3 months after the blanking period after AFCA using the LAW-stress[measured] and LAW-stress[AI] in cohort 1 and LAW-stress[AI] in cohort 2. LAW-stress[measured] was independently associated with non-paroxysmal AF (p < 0.001), diabetes (p = 0.012), vascular disease (p = 0.002), body mass index (p < 0.001), E/Em (p < 0.001), and mean LA voltage measured by electrogram voltage mapping (p < 0.001). The best-performing AI model had acceptable prediction power for predicting Q4-LAW-stress[measured] (area under the receiver operating characteristic curve 0.734). During 26.0 (12.0–52.0) months of follow-up, AF recurrence was significantly higher in the Q4-LAW-stress[measured] group [log-rank p = 0.001, hazard ratio 2.43 (1.21–4.90), p = 0.013] and Q4-LAW-stress[AI] group (log-rank p = 0.039) in cohort 1. In cohort 2, the Q4-LAW-stress[AI] group consistently showed worse rhythm outcomes (log-rank p < 0.001). A higher LAW-stress was associated with poorer rhythm outcomes after AFCA. AI was able to predict this complex but useful prognostic parameter using non-invasive parameters with moderate accuracy.

Abstract Background Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). Methods Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis. Results High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175–2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC. Conclusions Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.

Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.

Abstract Backgrounds Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn’s disease (CD). Methods A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. Results Median age of patients was 22.5 years (range, 15–49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months–54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). Conclusion Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

The molecular profile of cholangiocarcinoma (CC) remains elusive. The prognostic value of isocitrate dehydrogenase (IDH) mutations in CC is controversial, and there have been few relevant studies in Asian populations. In the present study, we investigated the frequency and prognostic significance of IDH mutations in Korean patients with CC. CC specimens were collected from patients who underwent surgical liver resection between 2004 and 2019. Clinical and pathological data were retrospectively reviewed from medical records. Mutational IDH profiling was performed by peptide nucleic acid-mediated PCR clamping in 206 surgical specimens; IDH-mutant samples were confirmed by next-generation sequencing (NGS). Of the 195 patients with CC, six (3.13%) were found to exhibit IDH1 (n = 5) or IDH2 (n = 1) mutations. Among patients with IDH1 mutations, four had R132C (c.394C>T) and one had R132G (c.394C>G) mutations. One patient had R172W (c.514A>T) mutations in IDH2. All IDH-mutant samples were of intrahepatic origin, and patients with IDH mutations had physiological to low serum levels of carbohydrate antigen 19-9 (CA19-9). No association between IDH mutation status and long-term survival outcomes was observed. The frequency of IDH mutations was considerably lower than the 10–20% reported in previous studies. The frequency and pattern of IDH mutations in CC are likely to vary among patients with different ethnicities. These findings suggest that characterization of the oncogenic mutation profile in different populations is of high clinical importance.

Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

Background and objectives: Obstructive sleep apnea (OSA) is closely associated with insulin resistance (IR) and is an independent risk factor for incident type 2 diabetes mellitus (T2DM). Most studies evaluate the correlation between OSA and IR in only obese or T2DM patients. Therefore, we tried to investigate the effect of OSA on metabolic syndrome and IR in the general healthy male population. Materials and Methods: 184 subjects who visited a preventive health examination program were recruited for this study. All subjects received overnight polysomnography by a portable device (Watch-PAT 200). We examined several metabolic parameters and a homeostasis model of assessment for insulin resistance index (HOMA-IR). The subjects were divided into three groups by AHI (Apnea-hyponea index): normal group (AHI < 5), mild OSA group (5 ≤ AHI < 15), and moderate-severe OSA group (AHI ≥ 15). They were also divided into two groups according to minimum oxygen saturation: low group, Min-SpO2 < 88%; and high group, Min-SpO2 ≥ 88%. Results: Parameters of metabolic syndrome, including waist circumference, systolic and diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol showed significant differences among the AHI groups. Furthermore, HOMA-IR showed significant differences among the AHI groups. Those parameters, including metabolic syndrome and HOMA-IR, also showed differences between Min-SpO2 groups. Conclusions: In summary, this study helps confirm that AHI is associated with HOMA-IR in the general male population. Furthermore, the severity of AHI correlated with the parameters of metabolic syndrome. Therefore, AHI might be an indicator for evaluating both T2DM and metabolic syndrome, even in the general male population.

Abstract Background Epithelial-mesenchymal transition (EMT), principally involving an E-cadherin to N-cadherin shift, linked to tumor invasion or metastasis, and therapeutic resistance in various human cancer. A growing body of recent evidence has supported the hypothesis that EMT play a crucial role in the invasive phenotype of gliomas. To evaluate the prognostic connotation of EMT traits in glioma, expression of E-cadherin and N-cadherin was explored in a large series of glioma patients in relation to patient survival rate. Methods Expressions of E- and N-cadherin were examined using immunohistochemical analysis in 92 glioma cases diagnosed at our hospital. These markers expressions were also explored in 21 cases of fresh frozen glioma samples and in glioma cell lines by Western blot analysis. Results Expression of E-cadherin was observed in eight cases (8.7%) with weak staining intensity in the majority of the immunoreactive cases (7/8). Expression of N-cadherin was identified in 81 cases (88.0%) with high expression in 64 cases (69.5%). Fresh frozen tissue samples and glioma cell lines showed similar results by Western blot analysis. There was no significant difference in either overall survival (OS) or progression-free survival (PFS) according to E-cadherin expression (P > 0.05). Although the OS rates were not affected by N-cadherin expression levels (P = 0.138), PFS increased in the low N-cadherin expression group with marginal significance (P = 0.058). The survival gains based on N-cadherin expression levels were significantly augmented in a larger series of publicly available REMBRANDT data (P

Dexmedetomidine is a highly selective α2-adrenoceptor agonist that demonstrates anxiolytic and analgesic properties without inducing respiratory compromise, which makes it a suitable agent for procedural sedation and imaging studies. In our current case reports, intravenous dexmedetomidine infusion was used to provide sedation to 2 pediatric patients over more than 20 sessions of radiation therapy. On both occasions, dexmedetomidine provided adequate sedation without respiratory depression. However, the required dosage increased with repeated radiation therapy sessions.

BACKGROUNDS: Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer. METHODS: We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining. RESULTS: Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival. CONCLUSIONS: These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D. [ABSTRACT FROM AUTHOR]

Various X-ray techniques are employed to investigate specimens in diverse fields. Generally, scattering and absorption/emission processes occur due to the interaction of X-rays with matter. The output signals from these processes contain structural information and the electronic structure of specimens, respectively. The combination of complementary X-ray techniques improves the understanding of complex systems holistically. In this context, we introduce a multiplex imaging instrument that can collect small-/wide-angle X-ray diffraction and X-ray emission spectra simultaneously to investigate morphological information with nanoscale resolution, crystal arrangement at the atomic scale and the electronic structure of specimens. [ABSTRACT FROM AUTHOR]

Background: The changes in blood viscosity can influence the shear stress at the vessel wall, but there is limited evidence regarding the impact on thrombogenesis and acute stroke. We aimed to investigate the effect of blood viscosity on stroke and the clinical utility of blood viscosity measurements obtained immediately upon hospital arrival. Methods: Patients with suspected stroke visiting the hospital within 24 h of the last known well time were enrolled. Point-of-care testing was used to obtain blood viscosity measurements before intravenous fluid infusion. Blood viscosity was measured as the reactive torque generated at three oscillatory frequencies (1, 5, and 10  rad/sec). Blood viscosity results were compared among patients with ischemic stroke, hemorrhagic stroke, and stroke mimics diagnosed as other than stroke. Results: Among 112 enrolled patients, blood viscosity measurements were accomplished within 2.4  ±  1.3  min of vessel puncture. At an oscillatory frequency of 10  rad/sec, blood viscosity differed significantly between the ischemic stroke (24.2  ±  4.9 centipoise, cP) and stroke mimic groups (17.8  ±  6.5  cP, p  <  0.001). This finding was consistent at different oscillatory frequencies (134.2  ±  46.3 vs. 102.4  ±  47.2 at 1  rad/sec and 39.2  ±  11.5 vs. 30.4  ±  12.4 at 5  rad/sec, Ps  <  0.001), suggesting a relationship between decreases in viscosity and shear rate. The area under the receiver operating curve for differentiating cases of stroke from stroke mimic was 0.79 (95% confidence interval, 0.69–0.88). Conclusion: Patients with ischemic stroke exhibit increases in whole blood viscosity, suggesting that blood viscosity measurements can aid in differentiating ischemic stroke from other diseases. [ABSTRACT FROM AUTHOR]