Highlights • NF-κB-derived inhibitor tripeptide, NF-κB-DVH, was envisioned to block dimerization of p50/p65. • Strong anti-inflammatory activity was resulted through suppressed NF-κB activation. • ...Prevention of photoaging processes was tested both in vitro and in vivo animal model. • This inhibitor tripeptide was proposed for anti-inflammation, anti-photoaging agent.
Respiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes a common respiratory disease. Despite serious pathological consequences with this virus, ...effective treatments for controlling RSV infection remain unsolved, along with poor innate immune responses induced at the initial stage of RSV infection. Such a poor innate defense mechanism against RSV leads us to study the role of alveolar macrophage (AM) that is one of the primary innate immune cell types in the respiratory tract and may contribute to protective responses against RSV infection. As an effective strategy for enhancing anti-viral function of AM, this study suggests the intranasal administration of
spore which induces expansion of AM in the lung with activation and enhanced production of inflammatory cytokines along with several genes associated with M1 macrophage differentiation. Such effect by spore on AM was largely dependent on TLR-MyD88 signaling and, most importantly, resulted in a profound reduction of viral titers and pathological lung injury upon RSV infection. Taken together, our results suggest a protective role of AM in RSV infection and its functional modulation by
spore, which may be a useful and potential therapeutic approach against RSV.
A novel three-dimensional (3D) scaffold of chemically unmodified hyaluronic acid (HA) with minimum cross-linkage was developed for the culture of chondrocytes, thereby to promote cartilage repair. ...The porous structure of the scaffold was observed by scanning electron microscopy (SEM), and the pore size was controlled by fabrication conditions including swelling time and composition of the HA matrix. Rabbit primary chondrocytes and human chondrocytic cell lines (C-20/A4) were cultured in the HA matrix to investigate whether they can be applied to construct the cartilage tissue
in vitro. The chondrocytes retained chondrocytic spherical morphology in this HA matrix. Moreover, results from the MTT assay showed good cellular viability within the HA matrix; optical density increased for up to 28 days, demonstrating that the cells continued to proliferate inside the HA matrix. Phenotypic analysis (RT-PCR, Alcian blue staining and quantification of s-GAG) showed that chondrocytes, when three-dimensionally cultured within the HA matrix, expressed transcripts encoding collagen type II and aggrecan, and produced sulfated glycosaminoglycans (s-GAG), indicating chondrogenic differentiation. The new HA matrix therefore appears as a potentially promising scaffold for the three-dimensional culture of chondrocytes for cartilage tissue engineering.
Abstract Background The added value of cardiac computed tomography (CT) with TEE for evaluating mechanical aortic valve (AV) dysfunction has not yet been investigated. The purposes of this study were ...to investigate the added value of cardiac CT for evaluation of mechanical AVs and diagnoses of pannus compared to transesophageal echocardiography (TEE), with surgical findings of redo-aortic valve replacement (AVR) used as a standard reference. Methods 25 patients who underwent redo-AVR due to mechanical AV dysfunction and cardiac CT before redo-AVR were included. The presence of pannus, encroachment ratio by pannus, and limitation of motion (LOM) were evaluated on CT. The diagnostic performance of pannus detection was compared using TEE, CT, and CT + TEE, with surgical findings as a standard reference. The added value of CT for diagnosing the cause of mechanical AV dysfunction was assessed compared to TTE + TEE. Results In two patients, CT analysis was not feasible due to severe metallic artifacts. On CT, pannus and LOM were found in 100% (23/23) and 60.9% (14/23). TEE identified pannus in 48.0% of patients (12/25). CT, TEE, and CT + TEE correctly identified pannus with sensitivity of 92.0%, 48.0%, and 92.0%, respectively (P = 0.002 for CT vs. TEE). In 11 of 13 cases (84.6%) with inconclusive or negative TEE results for pannus, CT detected the pannus. Among 13 inconclusive cases of TTE + TEE for the cause of mechanical AV dysfunction, CT suggested 6 prosthetic valve obstruction (PVO) by pannus, 4 low-flow low-gradient PVO, and one LOM without significant PVO. Conclusions Cardiac CT showed added diagnostic value with TEE in the detection of pannus as the cause of mechanical AV dysfunction.
Active control of defect structures and associated polarization switching in a ferroelectric material is achieved without compromising its ferroelectric properties. Based on dipolar interaction ...between defect dipole and polarization, the unique functionality of the defect dipole to control ferroelectric switching is visualized. This approach can provide a foundation for novel ferroelectric applications, such as high‐density multilevel data storage.
Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce ...moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke.
This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale MADRS ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498.
Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 13% patients in the placebo group vs 27 13% in the escitalopram group; odds ratio OR 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 14% vs 35 15%; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 6% patients who received placebo vs 14 6% who received escitalopram), muscle pain (16 7% vs ten 4%), and insomnia (12 5% vs 12 5%). Diarrhoea was more common in the escitalopram group (nine 4% patients) than in the placebo group (two 1% patients).
Escitalopram did not significantly reduce moderate or severe depressive symptoms in patients with acute stroke.
Dong-A Pharmaceutical and Ministry for Health, Welfare, and Family Affairs, South Korea.
Purpose
To determine the optimal maturation method to increase the yield of mature oocytes, especially for cancer patients with fewer chances of fertility preservation (FP) before gonadotoxic ...therapy.
Methods
A total of 373 cycles in 293 patients undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin‐releasing hormone (GnRH) antagonist protocol were enrolled. The control group (n = 225) received 250 µg of recombinant human chorionic gonadotropin (rhCG) while the study group (n = 148) received 250 µg of rhCG and 0.2 mg of triptorelin for triggering. Subgroup analyses were performed for stimulation cycles with diminished ovarian reserve (DOR; anti‐Müllerian hormone (AMH) levels <1.1 ng/ml, n = 86), with endometrioma (n = 104), or with breast cancer and endometrial cancer using 5 mg of letrozole during the COS cycles (n = 84).
Results
There was no significant difference in the baseline characteristics or the number of total and mature oocytes between the two groups. Subgroup analyses for women with endometrioma or DOR showed similar results. However, the dual trigger group had a significantly higher number of mature oocytes than the rhCG trigger group in breast and endometrial cancer patients using letrozole during the COS cycles (6.9 ± 6.0 vs. 4.6 ± 3.6, p = 0.034). The maturation rate was higher in the dual trigger group, although the difference was not statistically significant (59.3 ± 26.7 vs. 50.0 ± 28.0, p = 0.124).
Conclusions
Dual triggering can be an efficient maturation method to maximize the yield of mature oocytes in breast or endometrial cancer patients using letrozole‐combined GnRH antagonist protocol for FP.
The discrepancy between planimetered mitral valve area (MVA) and mean diastolic pressure gradient (MDPG) has not been studied extensively in patients with mitral stenosis. The purpose of the present ...study was to investigate differences in characteristics and outcomes after mitral valve replacement (MVR) between low- and high-MDPG groups in patients with very severe mitral stenosis (VSMS). The hypothesis was that the low-MDPG group would have different characteristics and would be associated with poor clinical outcomes after MVR.
In total, 140 patients who underwent isolated MVR because of pure VSMS (planimetered MVA ≤ 1.0 cm(2)) were retrospectively reviewed, and follow-up echocardiography was performed for ≥12 months after MVR. Patients were divided into two groups according to preoperative MDPG (low gradient LG, <10 mm Hg; high gradient HG, ≥10 mm Hg). Strain and strain rate analysis was performed using speckle-tracking echocardiography of the left ventricle before MVR in a subgroup of 56 patients.
There were 82 patients (59%) in the LG group and 58 patients (41%) in the HG group. The LG group was older and demonstrated a higher prevalence of female gender, diabetes mellitus, and atrial fibrillation (P < .05 for all). When comparing the LG and HG groups, the left atrial volume index was larger (105.1 ± 51.9 vs 87.8 ± 42.9 mL/m(2), P < .001), and strain rate during isovolumic relaxation of the left ventricle was lower (0.17 ± 0.08 vs 0.29 ± 0.09 sec(-1), P < .001) in the LG group. After MVR, the percentage left atrial volume index reduction after MVR was significantly smaller in the LG group (-29.9 ± 15.1% vs -43.5 ± 16.4%, P < .001). Persistent symptoms after MVR were more common in the LG group compared with the HG group (P = .004), even though preoperative functional class was similar between the groups.
Compared with those with HG VSMS, patients with LG VSMS were older, more often female, and more frequently had diabetes mellitus and atrial fibrillation. They also had greater impairment of isovolumic relaxation, less favorable left atrial reverse remodeling, and a greater risk for persistent symptoms after MVR. These data might suggest other concurrent mechanisms for left atrial enlargement and symptom development in LG VSMS, such as atrial fibrillation and diastolic dysfunction, as well as valvular stenosis.
Peripheral artery disease (PAD) is frequently present in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. This study assessed the impact of PAD on ...clinical outcome after TAVI.
A total of 115 patients who underwent TAVI were evaluated retrospectively. Patients were divided into PAD and non-PAD groups, with PAD defined as stenosis≥50% in lower extremity arteries. Immediate and late clinical outcomes were compared between the two groups.
PAD was present in 31.3% (36/115) of the patients undergoing TAVI. Compared to the non-PAD group, the PAD group had higher Society of Thoracic Surgeons' (STS) risk scores (8.83%±6.20% vs 6.23%±4.15%, p=0.039) and more frequent diagnoses of diabetes (52.8% vs 30.4%, p=0.021) and multi-vessel coronary artery disease (55.6% vs 29.1%, p=0.007). The PAD group also had higher incidence of major vascular complication (11.1% vs 1.3%, p=0.033), 30-day mortality (13.9% vs 1.3%, p<0.001), and subsequent 1-year (30.6% vs 3.8%, p<0.001) and 2-year (47.2% vs. 10.1%, p<0.001) all-cause mortality. PAD was identified as an independent predictor of increased 1-year mortality (hazard ratio HR 8.65; 95% confidence interval CI, 1.05–71.14, p=0.045) after TAVI along with high STS score (HR 11.18, 95% CI 1.36–92.04, p=0.025).
Presence of PAD was significantly associated with increased rates of major vascular complications as well as immediate and late mortality in patients undergoing TAVI. Assessment of PAD before TAVI is essential to choose an access strategy and to predict clinical results.
•Peripheral Artery Disease is common in transcatheter aortic valve implant patients.•PAD was associated with major vascular complications in TAVI patients (p=0.033).•PAD was associated with immediate and late mortality in TAVI patients (p<0.001).•PAD was an independent predictor of 1-year mortality after TAVI (p=0.025).•Assessment of PAD before TAVI is essential to determine procedure and clinical outcome.
BACKGROUND AND PURPOSE—We evaluated whether hemoglobin concentration at admission was associated with stroke recurrence and composite vascular events (stroke, myocardial infarction, and vascular ...death) in acute ischemic stroke.
METHODS—We collected data from patients with acute ischemic stroke or transient ischemic attack from a multicenter stroke registry database in Korea. The association of hemoglobin concentration with 1-year stroke recurrence and composite vascular events was evaluated with respect to age, presence of cerebral artery stenosis, stroke severity, and stroke subtype.
RESULTS—Hemoglobin levels were inversely associated with stroke recurrence and composite vascular events. One-year rates of stroke recurrence and composite vascular events were significantly higher in patients with anemia or moderate anemia. In multivariable analyses, moderate anemia remained an independent predictor of stroke recurrence (adjusted hazard ratio, 1.43 95% CI, 1.16–1.75) and composite vascular events (adjusted hazard ratio, 1.26 95% CI, 1.07–1.48). Moderate anemia increased the risk of composite vascular events in patients with mild-to-moderate stroke severity (National Institutes of Health Stroke Scale score <16, P=0.01 for interaction).
CONCLUSIONS—Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.
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