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Age-related macular degeneration (AMD) is one of the major causes of blindness in the elderly worldwide. Anti-vascular endothelial growth factor (VEGF) drugs have been widely used to treat the neovascular type of AMD (nAMD). However, VEGF acts not only as a pro-angiogenic factor but also as an anti-apoptotic factor in the eyes. In this study, we found that anti-VEGF drugs, including bevacizumab (Bev), ranibizumab (Ran), and aflibercept (Afl), induced epithelial-mesenchymal transition (EMT) in ARPE-19 cells in vitro, accompanied by the induction of CCN2, a potent pro-fibrotic factor. Similarly, intravitreal injection of Afl into mouse eyes resulted in EMT in the retinal pigmented epithelium (RPE). Co-treatment with CCN5, an anti-fibrotic factor that down-regulates CCN2 expression, significantly attenuated the adverse effects of the anti-VEGF drugs both in vitro and in vivo. Inhibition of the VEGF signaling pathway with antagonists of VEGF receptors, SU5416 and ZM323881, induced EMT and up-regulated CCN2 in ARPE-19 cells. Additionally, knock-down of CCN2 with siRNA abolished the adverse effects of the anti-VEGF drugs in ARPE-19 cells. Collectively, these results suggest that anti-VEGF drugs induce EMT in RPE through the induction of CCN2 and that co-treatment with CCN5 attenuates the adverse effects of anti-VEGF drugs in mouse eyes. [ABSTRACT FROM AUTHOR]

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to investigate the effects of each phytogenic feed additive (PFA; PFA1, bitter citrus extract; PFA2, a microencapsulated blend of thymol and carvacrol; PFA3, a mixture of bitter citrus extract, thymol, and carvacrol; PFA4, a premixture of grape seed, grape marc extract, green tea, and hops; PFA5, fenugreek seed powder) on the growth performance, nutrient digestibility, intestinal morphology, and immune response in weaned pigs infected with Escherichia coli (E. coli). Results: A total of 63 4-week-old weaned pigs were placed in individual metabolic cages and assigned to seven treatment groups. The seven treatments were as follows: 1) NC; basal diet without E. coli challenge, 2) PC; basal diet with E. coli challenge, 3) T1; PC + 0.04% PFA1, 4) T2; PC + 0.01% PFA2, 5) T3; PC + 0.10% PFA3, 6) T4; PC + 0.04% PFA4, 7) T5; PC + 0.10% PFA5. The experiments lasted in 21 d, including 7 d before and 14 d after the first E. coli challenge. In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F18 for 3 consecutive days. The PFA-added groups significantly increased (P < 0.05) average daily gain and feed efficiency and decreased (P < 0.05) the fecal score at d 0 to 14 post-inoculation (PI). Tumor necrosis factor α was significantly lower (P < 0.05) in the PFA-added groups except for T1 in d 14 PI compared to the PC treatment. The T3 had a higher (P < 0.05) immunoglobulin G and immunoglobulin A concentration compared to the PC treatment at d 7 PI. Also, T3 showed significantly higher (P < 0.05) villus height:crypt depth and claudin 1 expression in ileal mucosa, and significantly down-regulated (P < 0.05) the expression of calprotectin compared to the PC treatment. Conclusions: Supplementation of PFA in weaned pigs challenged with E. coli alleviated the negative effects of E. coli and improved growth performance. Among them, the mixed additive of bitter citrus extract, thymol, and carvacrol showed the most effective results, improving immune response, intestinal morphology, and expression of tight junctions. [ABSTRACT FROM AUTHOR]

The matricellular protein CCN5 exerts anti-fibrotic activity in hearts partly by inducing reverse trans-differentiation of myofibroblasts (MyoFBs) to fibroblasts (FBs). CCN5 consists of three structural domains: an insulin-like growth factor binding protein (IGFBP), a von Willebrand factor type C (VWC), and a thrombospondin type 1 (TSP-1). In this study, we set out to elucidate the roles of these domains in the context of the reverse trans-differentiation of MyoFBs to FBs. First, human cardiac FBs were trans-differentiated to MyoFBs by treatment with TGF-β; this was then reversed by treatment with recombinant human CCN5 protein or various recombinant proteins comprising individual or paired CCN5 domains. Subcellular localization of these recombinant proteins was analyzed by immunocytochemistry, cellular fractionation, and western blotting. Anti-fibrotic activity was also evaluated by examining expression of MyoFB-specific markers, α-SMA and fibronectin. Our data show that CCN5 is taken up by FBs and MyoFBs mainly via clathrin-mediated endocytosis, which is essential for the function of CCN5 during the reverse trans-differentiation of MyoFBs. Furthermore, we showed that the TSP-1 domain is essential and sufficient for endocytosis and nuclear localization of CCN5. However, the TSP-1 domain alone is not sufficient for the anti-fibrotic function of CCN5; either the IGFBP or VWC domain is needed in addition to the TSP-1 domain. [ABSTRACT FROM AUTHOR]

This paper presents a web-based three-dimensional (3D) navigation system for a spinal disease ontology using a 3D virtual human spine. The 3D navigation system consists of three main modules: a query module for finding spinal diseases and their causes and treatments from the spinal disease ontology via a web page, a 3D rendering module for rendering the virtual human spine on a web browser, and a visualization module to view the retrieved ontology information by connecting it with the virtual human spine. It was implemented using Virtuosos SPARQL, Java, JavaScript, Jena API, JDBC, AJAX, HTML5, WebGL, and SVG using a Virtuoso server on the Web via JSP web pages. Spine specialists can navigate and simulate spinal diseases using the 3D navigation system via virtual experiments based on the ontological interrelations, allowing them to make more accurate diagnoses of spinal diseases. [ABSTRACT FROM AUTHOR]

We established a fungal production platform by focusing on substrates of solid culture for conidial productivity and thermotolerance, and focusing on surfactants to effectively deliver fungal conidia to the Riptortus pedestris cuticles. First, to produce thermotolerant fungal conidia, 2 of each Beauveria bassiana and Metarhizium anisopliae isolates were cultured on 13 cereal substrates for 10 days. Overall, five substrates (millet, non-glutinous Italian foxtail millet, barley, glutinous Italian foxtail millet, and brown rice) produced greatest number of conidia with thermotolerant conidia. When the selected substrates were mixed with minerals, zeolite, perlite or vermiculite to reduce the amount of cereal grains, vermiculite combination showed relatively high conidial production compared to the other mineral combinations. Next, to efficiently deliver the fungal conidia to the cuticles of R. pedestris, six surfactants, CO-2.5, CO-12, LE-7, PE-61, TED-3, and siloxane were each combined with the fungal conidia. The 0.01% combination showed significantly increased insect mortality, which varied depending on isolate. Virulence tests against R. pedestris were performed with conidial suspensions of isolates to assess their virulence. As a result, isolates showed the highest virulence when a virulence test was conducted at 25°C, rather than 20°C, 30°C and 35°C. This work suggests that the combination of cereal grain substrates and vermiculite could be considered for economic conidial production with high thermotolerance, and the CO-12 surfactant is the most suitable for effective delivery to target insects, followed by the information on optimal temperature for virulence against R. pedestris. [ABSTRACT FROM AUTHOR]

Azole fungicides is one of the major fungicides in agricultural field. In this study, toxic effects of diniconazole (DIN), metconazole (MET), and tebuconazole (TEB) to radish leaves and roots were investigated using targeted metabolomics with gas chromatography-mass spectrometry (GC-MS/MS). Especially, the changes of functional chemicals, including phytosterols and glucosinolates evaluated. Radish leaves and roots were harvested after 7 days and 14 days from last exposure. In multivariate analysis, the experimental groups showed clear separation in PCA and PLS-DA score plots. Phytosterols and glucosinolates were significantly changed by azole fungicide. Six metabolic pathways which are affected by fungicides were selected and showed similar patterns regardless of the type of azole fungicide used. As a result, azole fungicide induces the defense mechanisms of plants and affects both primary and secondary metabolism. [Display omitted] • Azole fungicides induce metabolic changes in radish leaves and roots. • Primary metabolites tend to be decreased in leaves while they were increased in roots. • Phytosterol contents were changed by azole application. • Glucosinolates which relate to defense mechanism were increased. [ABSTRACT FROM AUTHOR]

This paper addresses how to determine a sufficient frame (sampling) rate for an optical motion tracking system using passive reflective markers. When using passive markers for the optical motion tracking, avoiding identity confusion between the markers becomes a problem as the speed of motion increases, necessitating a higher frame rate to avoid a failure of the motion tracking caused by marker confusions and/or dropouts. Initially, one might believe that the Nyquist-Shannon sampling rate estimated from the assumed maximal temporal variation of a motion (i.e. a sampling rate at least twice that of the maximum motion frequency) could be the complete solution to the problem. However, this paper shows that also the spatial distance between the markers should be taken into account in determining the suitable frame rate of an optical motion tracking with passive markers. In this paper, a frame rate criterion for the optical tracking using passive markers is theoretically derived and also experimentally verified using a high-quality optical motion tracking system. Both the theoretical and the experimental results showed that the minimum frame rate is proportional to the ratio between the maximum speed of the motion and the minimum spacing between markers, and may also be predicted precisely if the proportional constant is known in advance. The inverse of the proportional constant is here defined as the tracking efficiency constant and it can be easily determined with some test measurements. Moreover, this newly defined constant can provide a new way of evaluating the tracking algorithm performance of an optical tracking system. [ABSTRACT FROM AUTHOR]

Purpose: We calculated the cumulative sum analysis of an individual surgical learning curve for mitral valve reconstructive surgery to monitor quality control. Methods: Between April 2003 and March 2009, 25 consecutive patients underwent mitral valve reconstructive surgery for mitral regurgitation (MR). All operations were performed by a single surgeon. We analyzed the operative variables, mortality, and major morbidities and calculated the learning curve, using descriptive statistics and cumulative sum analysis based on the Japan SCORE calculator. Results: In this series, the Japan SCORE calculator predicted a 30-day operative mortality rate of 3.07 ± 3.48 % and a 30-day operative mortality and morbidity rate of 14.9 ± 9.58 %s. In reality, there was no operative or in-hospital death and the major postoperative morbidity rate was 6.0 % (two patients). The risk-adjusted cumulative sum analysis revealed that the learning curve for mortality and morbidity shifted downward below the lower confident interval for all the patients, on completion of mitral valve repair. Coefficient analysis revealed a significant negative correlation between the aortic cross-clamp time and the cardiopulmonary time and case load. There was no correlation between the operation time and the case load. Conclusions: Routine reconstructive mitral valve surgery for MR can be performed at the professionally permissive level from the beginning, even in low-volume case loads. [ABSTRACT FROM AUTHOR]

A focused source can provide an auditory illusion of a virtual source placed between the loudspeaker array and the listener. When a focused source is generated by time-reversed acoustic focusing solution, its use as a virtual source is limited due to artifacts caused by convergent waves traveling towards the focusing point. This paper proposes an array activation method to reduce the artifacts for a selected listening point inside an array of arbitrary shape. Results show that energy of convergent waves can be reduced up to 60 dB for a large region including the selected listening point. [ABSTRACT FROM AUTHOR]

Objectives: The surgical box lesion isolation of pulmonary veins and left atrium is recently reported to be superior to the conventional Cox maze IV procedure. The aim of this study is to investigate the midterm results of surgical box lesion ablation with the use of the bipolar radiofrequency energy performed at our institution. Methods: From April 2004 to December 2008, 35 patients underwent the surgical box lesion ablation using bipolar radiofrequency and were followed for mean 31 months ranging from 3 to 58 months. Results: There was no operative mortality. One patient (2.86%) needed electric cardioversion before discharge. One patient (2.86%) needed pacemaker implantation. At discharge, all patients were in normal sinus rhythm. During the follow-up period, the rate of sinus rhythm maintenance was 100%, the rate of freedom from antiarrhythmic medication was 42.9%, and the rate of freedom from thromboembolic episodes was 100%. Conclusions: The surgical box lesion ablation was a safe and effective procedure to terminate atrial fibrillation and restore sinus rhythm. (J Card Surg 2011;26:669-672) [ABSTRACT FROM AUTHOR]

Abstract: Objective: To better understand the mechanism of stroke during cardiopulmonary bypass, it is necessary to obtain information on the location of turbulence, wall pressure, and flow distribution within the aortic arch. Methods: Blood flow was numerically simulated using the finite element method in the following representative case: a curved arterial cannula was inserted into the anterior wall of the distal ascending aorta 2cm below the orifice of brachiocephalic artery. Perfusion was performed, with a bypass flow index of 2.5lmin−1 m−2. Computational grids, consisting of 1,493,297 tetrahedral elements, were generated. Results: The highest wall pressure (3104.8Pa) was observed at the superior-posterior wall of the aorta below the orifice of the brachiocephalic artery where jet flow impingement occurred. The maximum wall shear stress was 25.1Pa. High velocity vortex started below the orifice of the brachiocephalic artery. The turbulent flows continued along the posterior wall and then mainly flowed off into the left subclavian artery. Therefore, in the present case, an embolic event in the territory of the left subclavian artery could occur if a plaque was present at the superior-posterior wall of the aorta below the orifice of the brachiocephalic artery. The flow rates in each of the branches were 132, 613, 175, and 821ml/min for the right subclavian, right common carotid, left common carotid, and left subclavian artery, respectively. Conclusion: This study confirmed that blood flow during cardiopulmonary bypass can be simulated and visualized. Computational fluid dynamics could be applied in the future to assess an individual''s risk of stroke. Further multiple representative cases need to be simulated. [Copyright &y& Elsevier]

Side-to-side anastomosis was employed by just ten proportional stitches while performing distal anastomosis during coronary artery surgery. This technique is simple and quick. Here this simple technique is described in detail and the postoperative status of grafted conduits is reported. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, as the price of grains in feed increases worldwide, interest in new raw materials that can replace protein and fat sources is increasing. This study evaluated the effect of full-fat almonds (FFA) on broiler nutrition. In the study, the formulation of FFA as a raw material showed higher growth performance than the basic feed. This seems to be due to the high digestibility of protein and fat and the promotion of intestinal health through the reduction of harmful microorganisms in the intestine. Therefore, FFA can be used as a high-quality protein and fat substitute as a raw material for broiler feed. The purpose of this study was to evaluate the effect of full-fat almonds (FFA) as an alternative protein and fat source for broiler feed on broiler productivity, nutrient digestibility, blood characteristics, cecal-fecal microflora, and foot-pad dermatitis (FPD). A total of 96, one-day-old broiler chickens (Arbor Acres) with initial body weight 41.61 ± 0.36 g were placed in 16 cages. In each trial, four treatments were set up: a basal diet partially replacing animal fat with FFA 0% (Control, CON), a basal diet partially replacing animal fat with FFA 1% (T1), a basal diet partial replacing animal fat with FFA 2% (T2), a basal diet partially replacing animal fat with FFA 4% (T3). The experiment was conducted for a total of 4 weeks. Feed conversion ratio (FCR) was higher (p < 0.05) in the T3 group of broilers at weeks 0 to 1 than in the CON group of broilers. From weeks 3 to 4, and for the entire experimental period, FCR was lower (p < 0.05) in the T3 group of broilers than in the CON and T1 groups of broilers. The apparent ileal digestibility (AID) of the ether extract (EE) was higher (p < 0.05) in the T3 group than in the other treatment groups, and AID of crude protein (CP) was higher (p < 0.05) in the T3 group than in the CON group. The apparent total tract digestibility (ATTD) of EE was lower (p < 0.05) in the CON group than in the other treatment groups, and the ATTD of CP and energy was higher (p < 0.05) in the T3 group of broilers than in the CON group of broilers. The AID and ATTD of total amino acids were higher (p < 0.05) in the T3 group than in the other treatment groups. Blood cholesterol levels were lower (p < 0.05) in the T3 group of broilers than in the CON and T1 groups of broilers, and higher (p < 0.05) in the CON group of broilers than in the T2 and T3 groups of broilers. The amount of E. coli in the cecal and fecal was lower (p < 0.05) in the T3 group than in CON and T1 groups. FPD score was higher (p < 0.05) in the T3 group of broilers than in the CON group of broilers. In conclusion, replacing a partial of animal fat with at least 4% FFA in broiler diets can increase growth performance and nutrient digestibility in broiler nutrition. [ABSTRACT FROM AUTHOR]

• Quantitative approach to a daily plan-do-check-act (PDCA) cycle is challenging. • An ontology that addresses this problem for a foreman is proposed. • The ontology uses LOD400 objects and imaginary boundaries for quantitative approach. • A software prototype is developed based on the ontology. • Foremen tested the prototype and went through daily PDCA cycles with LOD400 objects. Level of development (LOD) 400 objects have the required information for definitively defining a list of materials and their quantities for a certain scope of construction work. Generating this information each day and operating LOD400 objects through the plan-do-check-act (PDCA) cycle on a daily basis could provide the quantitative basis for proactive and precise day-to-day field control. However, the high frequency of the cycle and the granularity of LOD400 make the process time-consuming and onerous for a foreman. The contribution of this research is an ontology that enables a foreman to go through the PDCA cycle on a daily basis with LOD400 objects and generate six information items (actual date of work completed, products built, location of products built, quantities of materials installed, number of workers that were on site, and performance metric) after the check step C of the PDCA cycle. The ontology was developed into a software prototype for field experiments and the results show that foremen can go through the daily PDCA cycle with LOD400 objects in 2 min and 47 s on average. The average usability score of the prototype was 95, which falls between "excellent" and "best imaginable" on the System Usability Scale (SUS). [ABSTRACT FROM AUTHOR]

Simple Summary: Piglets frequently experience post-weaning diarrhea (PWD) due to various stress factors at the weaning stage. PWD affects the growth performance and mortality of piglets, and they face various diseases due to reduced immunity response. A high dose of zinc oxide (ZnO) is used as a feed additive to prevent diarrhea occurrence and to promote immune system development. However, most of ZnO is discharged as manure, causing soil heavy metalization, accumulation in pork, increased and antimicrobial resistance. For this reason, research to reduce zinc excretion and prevent PWD through the supplementation of low-dose zinc in feed is essential; moreover, it is essential to develop alternatives to ZnO addition. Therefore, we hypothesized that different ratios of inorganic zinc and organic zinc at 1000 mg/kg or a low-protein diet with commercial feed additives containing either essential oils, protease, and xylanase (MFA) could replace high-dose ZnO by preventing diarrhea and improving growth performance, nutrient digestibility, and gut health. We found that inorganic and organic zinc at a ratio of 500:500 mg/kg and a low-protein diet with essential oil, protease, and xylanase can be used to replace medical ZnO in weaned piglet diets. One hundred twenty weaned piglets (9.34 ± 0.74 kg) were used in a four-week experiment to investigate the effects of replacing medical ZnO with a different ratio of inorganic and organic zinc (IZ:OZ) or a low-crude-protein diet (LP) with mixed feed additives (MFAs) in the weaned piglets' diet. The dietary treatments included a control (CON), T1 (T1; ZnO 1000 mg/kg), T2 (IZ:OZ 850:150), T3 (IZ:OZ 700:300), T4 (IZ:OZ, 500:500), and T5 (LP with MFAs (0.1% essential oils + 0.08% protease + 0.02% xylanase)). The growth performance was decreased (p < 0.05) in the CON treatment compared with the T4 treatment. The diarrhea incidence was decreased (p < 0.05) in the T4 and the T5 treatment compared with the CON and the T1 treatments. The apparent total tract digestibility (ATTD) of nutrients were increased (p < 0.05) in the T4 and T5 treatments compared with the CON, T1, and T2 treatments. The T4 treatment had a higher (p < 0.05) ATTD of zinc than the T1, T2, and T3 treatments. The fecal microflora was improved (p < 0.05) in the T5 treatment compared with the CON and T3 treatments. In conclusion, IZ:OZ 500:500 could improve growth performance, nutrient digestibility, and zinc utilization while reducing diarrhea incidence in weaned piglets. Moreover, LP with MFA could replace medical ZnO. [ABSTRACT FROM AUTHOR]

A series of sulfonated poly(arylene ether sulfone) block copolymers with aliphatic chains (SPAES-LA) to lend structural flexibility in the polymer backbone have been synthesized to prepare proton exchange membranes (PEMs) showing improved electrochemical performance and dimensional/oxidative stabilities. The SPAES-LAs, bearing different hydrophilic/hydrophobic segment lengths, are prepared via polycondensation and sulfonation reactions. The sulfonation reaction occurs in specific fluorenylidene units by using chlorosulfonic acid. The SPAES-LA membrane, fabricated by solvent casting method, exhibits remarkable dimensional/thermal stabilities. Moreover, proton conductivity of as-prepared SPAES-LA membranes demonstrates significant improvement with expansion of ion clusters which is due to the increased hydrophilic volume ratio. In particular, the SPAES-LA-X12Y28 membrane exhibited heightened proton conductivity of 158.4 mS cm−1 as well as suitable dimensional stability and durability towards radical oxidation, due to an effective well-defined hydrophilic-hydrophobic interface. Furthermore, H 2 /O 2 fuel cell performance using SPAES-LA-X12Y28 membrane achieves a maximum power density of 232.02 mW cm−2, a result which points out that SPAES-LA membranes show great potential for applications of polymer electrolyte membrane. Image 1 • The block copolymers are synthesized via controlling oligomer lengths. • The fabricated membranes show desirable thermo-oxidative stability. • The membranes showed high physio-chemical properties. • The as-prepared membranes exhibit high ionic conductivity and unit-cell performance. [ABSTRACT FROM AUTHOR]

Amine functionalized carbon nanotube (ANCT) is applied as an inorganic potential proton conducting material embedded in a sulfonated poly(ether ether ketone) (SPEEK) matrix. The morphological, structural, thermomechanical, physiochemical and electrochemical properties of SPEEK/ACNT composite were investigated and compared to obtained results from bare SPEEK. The synthesized ACNT-incorporated SPEEK membrane have uniform and dense morphology and exhibit improved properties as proton exchange membrane (PEM); for example, SPEEK/ACNT possessed higher thermal stability and tensile strength than SPEEK alone. The amine functionalized structure of ACNT is assumed to be one of critical factors resulting in higher performance of SPEEK/ACNT membrane, since it can induce acid-base conducting networks between ACNT and SPEEK matrix, which would improve water uptake and proton conductivity while lowering ion exchange capacity of membrane. When used in 20% relative humidity, a polymer electrolyte fuel cell (PEFC) with SPEEK/ACNT membrane is found to exhibit much higher performance than a PEFC with bare SPEEK, suggesting the potential use of SPEEK/ACNT membrane as PEM. Proton hopping mechanism between acid-base networks in SPEEK/ACNT composite. Image 1 • ACNT was employed as inorganic potential filler to prepare SPEEK/ACNT composite. • Addition of ACNT to SPEEK resulted in improved physiochemical and thermomechanical properties. • Optimized SPEEK/ACNT (1.5 wt%) exhibited improved PEFC performance under 20% RH while holding excellent durability compared to bare SPEEK. [ABSTRACT FROM AUTHOR]

A 20-year-old Korean woman presented in August 1999 with a 3-month history of multiple, tiny papules on the periorbital and malar areas (Fig. 1a). She had noted hyperhidrosis for the preceding 6 months, even at room temperature. She had been well and had received no medication prior to her first visit to our clinic. Physical examination showed yellow colored, translucent, small papules, as well as finger tremor, exophthalmos, and a goiter. Histologic examination demonstrated cystic structures in the dermis lined with two layers of cuboidal epithelial cells (Fig. 2). The epidermis was normal and the rete ridges were partially effaced. Immunohistochemical studies revealed that the epithelial cells of the cyst wall were carcinoembryonic antigen (CEA) positive but S-100 protein negative. Because a goiter and finger tremor were noted on physical examination, hyperthyroidism was suspected. Thyroid function test results were: triiodothyronine (T3 ), 8.0 ng/mL (normal range, 0.7–1.9 ng/mL); free thyroxine (T4 ), 8.1 ng/mL (0.7–1.9 ng/mL); T4 , 35 µg/dL (6.0–11.8 µg/dL); thyroid-stimulating hormone (TSH), 0.04 IU/mL (0.25–4.0 IU/mL); positive for anti-TSH receptor antibody. On the basis of these findings, the patient was diagnosed with Graves’ disease and treated with methimazole, 40 mg/day. As the patient's symptoms improved, the therapeutic dose was decreased to 20 mg/day. Four months after the beginning of treatment, the free T4 and T3 values had returned to the normal range (Table 1). The skin lesions, finger tremor, and hyperhidrosis had also disappeared. Exophthalmos was improved, but still present (Fig. 1b). [ABSTRACT FROM AUTHOR]

This paper describes an active silencer system for low-frequency noise in water-filled pipes, with implementation in marine vessels and structures in mind. Active noise control in underwater environment has its unique challenges arising from bubbles. In this light the effect of bubbles on active noise control in water-filled pipes is explored, and a design guideline for a robust active silencer is proposed. The silencer consists of an underwater sound source, an error hydrophone, and an electronic controller programmed with an adaptive filter. The adaptive filter is updated using the filtered-x least mean square algorithm. Estimation of the incoming noise is performed using an adaptive notch filter. The performance of the active silencer is tested for pure tone noises below 500 Hz in a water-filled pipe connected to a reservoir. Notable reduction of noise is achieved with varying degrees of success at different bubble fractions. [ABSTRACT FROM AUTHOR]

Background: Cardiac fibrosis (CF) is associated with increased ventricular stiffness and diastolic dysfunction and is an independent predictor of long-term clinical outcomes of patients with heart failure (HF). We previously showed that the matricellular CCN5 protein is cardioprotective via its ability to inhibit CF and preserve cardiac contractility.Objectives: This study examined the role of CCN5 in human heart failure and tested whether CCN5 can reverse established CF in an experimental model of HF induced by pressure overload.Methods: Human hearts were obtained from patients with end-stage heart failure. Extensive CF was induced by applying transverse aortic constriction for 8 weeks, which was followed by adeno-associated virus-mediated transfer of CCN5 to the heart. Eight weeks following gene transfer, cellular and molecular effects were examined.Results: Expression of CCN5 was significantly decreased in failing hearts from patients with end-stage heart failure compared to nonfailing hearts. Trichrome staining and myofibroblast content measurements revealed that the established CF had been reversed by CCN5 gene transfer. Anti-CF effects of CCN5 were associated with inhibition of the transforming growth factor beta signaling pathway. CCN5 significantly inhibited endothelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, which are 2 critical processes for CF progression, both in vivo and in vitro. In addition, CCN5 induced apoptosis in myofibroblasts, but not in cardiomyocytes or fibroblasts, both in vivo and in vitro. CCN5 provoked the intrinsic apoptotic pathway specifically in myofibroblasts, which may have been due the ability of CCN5 to inhibit the activity of NFκB, an antiapoptotic molecule.Conclusions: CCN5 can reverse established CF by inhibiting the generation of and enhancing apoptosis of myofibroblasts in the myocardium. CCN5 may provide a novel platform for the development of targeted anti-CF therapies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: It is widely accepted that both valve and cardiac functions are closely correlated. In order to investigate the relationship between the valve and cardiac functions, we developed a model of an isolated working heart with crystalloid perfusate in swine. We investigated the feasibility of this model to evaluate the precise left ventricular function using the pressure–volume relationship and metabolic measurement. Another objective was as a trial for the imaging and analysis of valvular interventions with a high-speed digital camera on this model. Methods: Six isolated working hearts were subjected in the pressure–volume study, and additional three hearts were used in the valve imaging study. Measurement of the pressure–volume relationship was undertaken in situ before the heart was removed, and on the working heart mode during the initial 30min as the baseline, and at every 60min. Lactate levels were measured at every stage in the working heart mode. Mitral valve interventions were performed in three hearts, and valve motions were observed by a high-speed digital camera via the left ventricle. Results: The end-systolic elastance maintained a baseline level (5.17±2.25) until 180min and decreased at 240min (3.97±1.97, NS) and 300min (2.85±1.29, P&#60;0.01) of the working heart mode as compared with baseline. The Tau maintained a constant level until 180min and increased at 240min (62.2±13.3, NS) and 300min (85.5±43.4, P&#60;0.05) as compared with baseline (50.3±13.6). The slope of the end-diastolic pressure–volume relationship gradually increased with no significance until 180min and increased significantly (0.147±0.066, P&#60;0.01 vs 0.067±0.041 at baseline). Lactate increased accumulatively. The total heart energy was reduced from the initial phase of the working heart mode. The valves were well captured by the high-speed digital camera. Conclusions: The systolic and diastolic functions of an isolated heart were preserved at an acceptable level for 180min. The practical reliability of the swine working heart model was demonstrated. This model will be used reliably for the investigation of the interaction of valve and cardiac functions. [Copyright &y& Elsevier]

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)-6 and IL-8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL-6 concentration increased to 128.4 ± 20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1 ± 48.2 pg/ml, p < 0.02). The blood IL-8 concentration was not significantly different than that of adults. The total amounts of excreted IL-6 in the ultrafiltrate and urine during CPB were 11.5 ± 0.32 pg/kg and 0.32 ± 0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL-8 in the ultrafiltrate and urine were 4.64 ± 0.69 pg/kg and 1.92 ± 0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone. [ABSTRACT FROM AUTHOR]

Simple Summary: Piglets, especially at the weaning stage, are highly susceptible to various diseases due to an incomplete immune system development and stress responses. Post-weaning diarrhea has a significant impact on piglet growth rate and mortality, resulting in economic losses to the swine industry. Zinc oxide (ZnO) is widely used as a weaning diet supplement in the swine industry to prevent diarrheal diseases and promote immune system development. Despite the recently demonstrated beneficial effects of ZnO, many efforts have been made to reduce its excessive use in piglets owing to environmental pollution and toxic effects on tissues; thus, the need for an effective alternative ZnO form, which promotes zinc utilization, has been gaining attention. However, we do not completely understand the mode of action of ZnO alternatives or the amount required to exert positive effects on weaned piglets. Therefore, we conducted this study to evaluate the effects of different forms of ZnO alternatives (ZnO chelate with glycine (chelate-ZnO) and nanoparticle-sized ZnO (nano-ZnO)) on diarrhea score, nutrient digestibility, zinc utilization, intestinal immune profiles, and fecal microflora on piglets, together with a comparison of the standard ZnO treatment. We found that 200 ppm Nano-ZnO had similar positive effects on weaned piglets compared with 2500 ppm ZnO and therefore is a promising alternative to ZnO. Twenty weaned piglets with initial body weight of 6.83 ± 0.33 kg (21 day of age, LYD) were randomly assigned to four treatments for a two-week feeding trial to determine the effects of different dietary zinc on nutrient digestibility, intestinal health, and microbiome of weaned piglets. The dietary treatments included a negative control (CON), standard ZnO (ZnO, 2500 ppm), zinc chelate with glycine (Chelate-ZnO, 200 ppm), and nanoparticle-sized ZnO (Nano-ZnO, 200 ppm). At 0 to 1 week, the diarrhea score was decreased in the CON group compared with the ZnO, Chelate-ZnO, and Nano-ZnO group. In overall period, the ZnO and Nano-ZnO groups exhibited improved diarrhea scores compared to the CON group. The apparent total tract digestibility of dry matter and gross energy was the lowest in the CON group after one week. Compared to the ZnO group, the chelate-ZnO group exhibited higher proportion of T-bet+ and FoxP3+ T cells and the nano-ZnO group had higher numbers of RORgt+ and GATA3+ T cells in the mesenteric lymph nodes. ZnO group increased IL-6 and IL-8 levels in the colon tissues and these positive effects were observed in both chelate ZnO and nano-ZnO groups with lower level. The 16S rRNA gene analysis showed that the relative abundance of Prevotella was higher in the ZnO-treated groups than in the CON group and that of Succinivibrio was the highest in the nano-ZnO group. The relative abundance of Lactobacillus increased in the ZnO group. In conclusion, low nano-ZnO levels have similar effects on nutrient digestibility, fecal microflora, and intestinal immune profiles in weaning pigs; thus, nano-ZnO could be used as a ZnO alternative for promoting ZnO utilization and intestinal immunity. [ABSTRACT FROM AUTHOR]