Search

Hybrids of carbon nanotubes (CNTs) and poly(3,4-ethylenedioxythiophene) (PEDOT) treated by tetrakis(dimethylamino)ethylene (TDAE) have large n-type voltages in response to temperature differences. The reduced carrier concentration by TDAE reduction and partially percolated CNT networks embedded in the PEDOT matrix result in high thermopower and low thermal conductivity. The high electron mobility in the CNTs helps to minimally reduce the electrical conductivity of the hybrid, resulting in a large figure-of-merit., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To determine the B-type natriuretic peptide (BNP) level in pediatric septic patients, and to investigate its association with cardiovascular dysfunction and clinical outcome., Methods: Pediatric patients with sepsis or septic shock were prospectively enrolled in our pediatric intensive care unit (PICU). On day 1 of admission, plasma BNP levels were measured at the time-point of echocardiography. Myocardial dysfunction was defined as left ventricular fractional shortening (FS) < 30%. Inotropic support was quantified by inotropic scores and disease severity was assessed by Pediatric Risk of Mortality (PRISM) III scores. Therafter, associations between BNP levels and clinical parameters were analyzed., Results: There were 94 patients (mean: 5.6 yr, range: 2 mo-17 yr) that were consecutively enrolled in this study. The median BNP level was 127 pg/ml (range: 5 to 4950 pg/ml). BNP levels were correlated with PRISM III (rho = 0.36, p = 0.001) and C-reactive protein level (r = 0.39, p = 0.001). The median BNP levels were not only higher in patients with septic shock (n = 34) than those with sepsis (n = 58) (213 vs. 54 pg/ml, p = 0.0004), but also higher in patients with myocardial dysfunction (n = 18) than those with preserved myocardial function (n = 66) (765 vs. 65 pg/ml, p < 0.001). We also found that BNP levels correlated negatively with FS (r = -0.56, p < 0.001) and positively with inotropic scores (r = 0.34, p = 0.04). Most importantly, the median BNP levels were higher in non-survivors (n = 13) than survivors (n = 81) (367 vs. 106 pg/ml, p = 0.003)., Conclusions: BNP levels are elevated in pediatric septic patients early in the disease course, and increased levels are associated with cardiovascular dysfunction and worse clinical outcome., Key Words: B-type natriuretic peptide; Cardiac function; Pediatric; Sepsis; Septic shock.

Objective: To examine the prevalence and modalities of complementary and alternative medicine (CAM) use in children with cancer and sickle cell disease; the reasons for use of CAM; and the use of CAM before, during, and after treatment in children with cancer., Methods: This single-center, observational study administered caregivers a written questionnaire regarding the use of CAM therapies., Results: A total of 101 caregivers completed questionnaires. Including prayer, total CAM use in oncology and sickle cell disease was 64% and 63%, respectively. Non-prayer CAM use was 30% in oncology and 23% in sickle cell disease. Of respondents who reported using any CAM, the three most commonly used types were prayer (62.3% oncology; 60.0% sickle cell disease), vitamins/minerals (14.8% oncology; 10.0% sickle cell disease), and massage (9.8% oncology; 7.5% sickle cell disease). The primary reasons for using CAM were to provide hope, to improve quality of life, and to lessen adverse effects. In oncology patients, CAM use tended to increase during treatment compared with before and after treatment., Conclusions: The reported prevalence of non-prayer CAM use was lower (23%-30%) in this sample than has been reported in national samples or other geographic regions of the United States. Nonetheless, participants reported many positive reasons for using CAM, including to gain hope, improve quality of life, and control pain. Thus, CAM use appears to be an important aspect of medical care for many pediatric hematology/oncology families and should be a consideration when providers are discussing treatment and quality of care with families.

Background: Persistent patent ductus arteriosus (PDA) during hospitalization is thought to be associated with adverse pulmonary outcomes in very preterm infants. This observational study aimed to compare the lung function in very preterm infants with and without PDA at discharge., Methods: Very preterm infants, admitted to our neonatal intensive unit, who required respiratory support soon after birth and had undergone a lung function test at discharge, were enrolled. Infants with a need for positive-pressure support (either an invasive ventilator, or nasal continuous positive airway pressure without oxygen) or supplemental oxygen at a postmenstrual age of 36 weeks were defined as having bronchopulmonary dysplasia (BPD). Echocardiography was performed weekly for each of the very preterm infants with PDA to confirm closure of the PDA. The data were collected retrospectively., Results: Fifty-two very preterm infants received lung function tests before discharge during the study period, 28 of whom had PDA and received conservative management, and 20 who did not. The other 4 infants who were given active treatment for PDA were excluded. Gestational age was significantly smaller in the PDA group than in the no-PDA group (27.1 ± 2.0 vs. 28.6 ± 1.6 weeks, p = 0.009). Birth weight did not differ significantly in those with and those without PDA (0.98 ± 0.26 vs. 1.12 ± 0.26 kg, p = 0.074). Significantly more infants with PDA had BPD (p = 0.002) and required respiratory support for a longer period (p = 0.001) than those without PDA. However, functional residual capacity (ml/kg) at discharge was comparable between the two groups after adjusting for gestational age and postmenstrual age at testing (21.6 ± 8.4 vs. 21.5 ± 6.7 ml/kg, p = 0.894). Other lung function test parameters were also comparable., Conclusion: Under a definition of BPD (including infants needing CPAP but without oxygen) other than the conventional definition, the very preterm infants in our study who received conservative management for PDA had a higher percentage of BPD than the infants without PDA. The parameters of the lung function test and lung clearance index were comparable between these two groups at discharge.

Phosphodiesterase (PDE) inhibitors have been suggested as a possible candidate for the treatment of osteopenia, including osteoporosis. KMUP-1 is a novel xanthine derivative with inhibitory activities on the PDE 3, 4, and 5 iso-enzymes to suppress the degradation of cAMP and cGMP. This study aimed to investigate the effect of KMUP-1 on osteoblast differentiation and the underlying cellular and molecular mechanisms. Primary osteoblasts and osteoblastic MC3T3-E1 cells were examined. KMUP-1 enhanced alkaline phosphatase (ALP) activity and mineralization compared to untreated controls in primary osteoblasts and MC3T3-E1 cells. KMUP-1 also increased the mRNA expression of the osteoblastic differentiation markers, including collagen type 1a, ALP, osteocalcin, osteoprotegerin, BMP-2, and Runx2, a key transcription regulator for osteoblastic differentiation. The osteogenic effect of KMUP-1 was abolished by BMP signaling inhibitor, noggin. Furthermore, we found that KMUP-1 upregulated Smad1/5/8 phosphorylations with subsequent BRE-Luc activation confirmed by transient transfection assay. In addition, KMUP-1 inactivated glycogen synthase kinase-3β (GSK-3β), with associated nuclear translocation of β-catenin. Co-treatment with H89 and KT5823, cAMP and cGMP pathway inhibitors, respectively, reversed the KMUP-1-induced activations of Smad1/5/8, β-catenin, and Runx2. The findings demonstrate for the first time that KMUP-1 can promote osteoblast maturation and differentiation in vitro via BMP-2/Smad1/5/8 and Wnt/β-catenin pathways. These effects are mediated, in part, by the cAMP and cGMP signaling. Thus, KMUP-1 may be a novel osteoblast activator and a potential new therapy for osteoporosis., (© 2015 Wiley Periodicals, Inc.)

Background: Iron plays a pivotal role in the pathogenesis of Trichomonas vaginalis, the causative agent of highly prevalent human trichomoniasis. T. vaginalis resides in the vaginal region, where the iron concentration is constantly changing. Hence, T. vaginalis must adapt to variations in iron availability to establish and maintain an infection. The free radical signaling molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been proven to participate in iron deficiency in eukaryotes. However, little is known about the roles of these molecules in iron-deficient T. vaginalis., Methods: T. vaginalis cultured in iron-rich and -deficient conditions were collected for all experiments in this study. Next generation RNA sequencing was conducted to investigate the impact of iron on transcriptome of T. vaginalis. The cell viabilities were monitored after the trophozoites treated with the inhibitors of nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining., Results: We demonstrated that NO rather than ROS accumulates in iron-deficient T. vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO production is through a proteasome and arginine dependent pathway. We found that the inhibition of proteasome activity shortened the survival of iron-deficient cells compared with untreated iron-deficient cells. Surprisingly, the addition of arginine restored both NO level and the survival of proteasome-inhibited cells, suggesting that proteasome-derived NO is crucial for cell survival under iron-limited conditions. Additionally, NO maintains the hydrogenosomal membrane potential, a determinant for cell survival, emphasizing the cytoprotective effect of NO on iron-deficient T. vaginalis. Collectively, we determined that NO produced by the proteasome prolonged the survival of iron-deficient T. vaginalis via maintenance of the hydrogenosomal functions., Conclusion: The findings in this study provide a novel role of NO in adaptation to iron-deficient stress in T. vaginalis and shed light on a potential therapeutic strategy for trichomoniasis.

Objective: We conducted this nationwide study to examine the epidemiology of hyperlipidemia among Taiwanese patients with bipolar disorder., Methods: We used a random sample of 766,427 subjects who were ≥18 years old in 2005. Subjects with at least one primary diagnosis of bipolar disorder were identified. Individuals with a primary or secondary diagnosis of hyperlipidemia or medication treatment for hyperlipidemia were also identified. We compared the prevalence of hyperlipidemia in patients with bipolar disorder with the general population in 2005. Furthermore, we investigated this cohort from 2006 to 2010 to detect the incident cases of hyperlipidemia., Results: The prevalence of hyperlipidemia in patients with bipolar disorder was higher than that of the general population [13.5% vs. 7.9%; odds ratio, 1.75; 95% confidence interval (CI), 1.52-2.02] in 2005. The average annual incidence of hyperlipidemia in patients with bipolar disorder was also higher than that of the general population (4.37% vs. 2.55%; risk ratio, 1.66; 95% CI, 1.47-1.87) from 2006 to 2010., Conclusions: Patients with bipolar disorder had a higher prevalence and incidence of hyperlipidemia compared with the general population. Patients with bipolar disorder coexisting hypertension exhibited a higher likelihood of hyperlipidemia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner. In addition, KMUP-1 prevented ET-1-induced intracellular reactive oxygen species generation determined by the DCFH-DA assay in cardiomyocytes. KMUP-1 also attenuated phosphorylation of ERK1/2 and Akt/GSK-3β, and activation of calcineurin/NFATc4 and RhoA/ROCK pathways induced by ET-1. Furthermore, we found that the expression of heme oxygenase-1 (HO-1), a stress-response enzyme implicated in cardio-protection, was up-regulated by KMUP-1. Finally, KMUP-1 attenuated ET-1-stimulated activator protein-1 DNA binding activity. In conclusion, KMUP-1 attenuates cardiomyocyte hypertrophy induced by ET-1 through inhibiting ERK1/2, calcineurin/NFATc4 and RhoA/ROCK pathways, with associated cardioprotective effects via HO-1 activation. Therefore, KMUP-1 may have a role in pharmacological therapy of cardiac hypertrophy.

Composed exclusively of organic components, polyaniline (PANi), graphene, and double-walled nanotubes (DWNTs) are alternately deposited from aqueous solutions using a layer-by-layer assembly. The 40 quadlayer thin film (470 nm thick) exhibits electrical conductivity of 1.08 × 10(5) S m(-1) and a Seebeck coefficient of 130 μV K(-1) , producing a thermoelectric power factor of 1825 μW m(-1) K(-2) ., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, solid-state light-emitting electrochemical cells (LECs) based on ionic transition metal complexes (iTMCs) have attracted much research interest since they have the advantages of a simple device structure, a low operation voltage and compatibility with air-stable electrodes. These properties enable LECs to be cost-effective, versatile and power-efficient organic light-emitting sources. However, it is generally not easy to modify the molecular structure to achieve balanced carrier mobilities without altering the photoluminescence quantum yield of the iTMC. Furthermore, the carrier balance and the consequent device efficiency of single-layered LECs would not be easy to optimize since no carrier injection and transport layers can be used. In this perspective, some reported techniques to improve carrier balance of LECs based on iTMCs are described and reviewed. The importance and impact of these studies are highlighted. The effects on device lifetime and turn-on time because of employing these techniques to improve the carrier balance are also discussed. This perspective concludes that even with electrochemically doped layers, improving the carrier balance of LECs would be required for realizing efficient electroluminescent emission from simple-structure organic light-emitting sources.

Background: Glioblastoma (GBM) is poorly responsive to current chemotherapy. The nuclear transporter exportin 1 (XPO1, CRM1) is often highly expressed in GBM, which may portend a poor prognosis. Here, we determine the efficacy of novel selective inhibitors of nuclear export (SINE) specific to XPO1 in preclinical models of GBM., Methods: Seven patient-derived GBM lines were treated with 3 SINE compounds (KPT-251, KPT-276, and Selinexor) in neurosphere culture conditions. KPT-276 and Selinexor were also evaluated in a murine orthotopic patient-derived xenograft (PDX) model of GBM. Cell cycle effects were assayed by flow cytometry in vitro and immunohistochemistry in vivo. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase 3/7 activity assays., Results: Treatment of GBM neurosphere cultures with KPT-276, Selinexor, and KPT-251 revealed dose-responsive growth inhibition in all 7 GBM lines [range of half-maximal inhibitory concentration (IC50), 6-354 nM]. In an orthotopic PDX model, treatment with KPT-276 and Selinexor demonstrated pharmacodynamic efficacy, significantly suppressed tumor growth, and prolonged animal survival. Cellular proliferation was not altered with SINE treatment. Instead, induction of apoptosis was apparent both in vitro and in vivo with SINE treatment, without overt evidence of neurotoxicity., Conclusions: SINE compounds show preclinical efficacy utilizing in vitro and in vivo models of GBM, with induction of apoptosis as the mechanism of action. Selinexor is now in early clinical trials in solid and hematological malignancies. Based on these preclinical data and excellent brain penetration, we have initiated clinical trials of Selinexor in patients with relapsed GBM., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor that promotes pulmonary artery smooth muscle cell (PASMC) proliferation. 5-HT-induced K(+) channel inhibition increases [Ca(2+)]i in PASMCs, which is a major trigger for pulmonary vasoconstriction and development of pulmonary arterial hypertension (PAH). This study investigated whether KMUP-1 reduces pulmonary vasoconstriction in isolated pulmonary arteries (PAs) and attenuates 5-HT-inhibited K(+) channel activities in PASMCs. In endothelium-denuded PA rings, KMUP-1 (1 μM) dose-dependently reduced 5-HT (100 μM) mediated contractile responses. Responses to KMUP-1 were reversed by K(+) channel inhibitors (TEA, 10 mM, 4-aminopyridine, 5 mM, and paxilline, 10 μM). In primary PASMCs, KMUP-1 also dose-dependently restored 5-HT-inhibited voltage-gated K(+)-channel (Kv1.5 and Kv2.1) and large-conductance Ca(2+)-activated K(+)-channel (BKCa) proteins, as confirmed by immunofluorescent staining. Furthermore, 5-HT (10 μM)-inhibited Kv1.5 protein was unaffected by the PKA inhibitor KT5720 (1 μM) and the PKC activator PMA (1 μM), but these effects were reversed by KMUP-1 (1 μM), 8-Br-cAMP (100 μM), chelerythrine (1 μM), and KMUP-1 combined with a PKA/PKC activator or inhibitor. Notably, KMUP-1 reversed 5-HT-inhibited Kv1.5 protein and this response was significantly attenuated by co-incubation with the PKC activator PMA, suggesting that 5-HT-mediated PKC signaling can be modulated by KMUP-1. In conclusion, KMUP-1 ameliorates 5-HT-induced vasoconstriction and K(+)-channel inhibition through the PKC pathway, which could be valuable to prevent the development of PAH.

Solid-state white light-emitting electrochemical cells (LECs) have attracted research attention owing to their advantages of simple device structure, low operation voltage and compatibility with solution processes. In this work, we demonstrate a simple approach to obtain white electroluminescence (EL) from non-doped LECs based on a blue-emitting complex. With a relatively thicker emissive layer, red emission can be additionally enhanced by the microcavity effect when the recombination zone moves to appropriate positions. Hence, white EL can be harvested by combining blue emission from the complex and red emission from the microcavity effect. These non-doped white LECs show external quantum efficiencies and power efficiencies up to 5% and 12 lm W(-1), respectively. These results show that efficient white EL can be obtained in simple non-doped LECs.

Background: Pneumonia is a life-threatening disease in children. With the current lack of universal diagnostic criteria, the diagnosis is usually made on clinical manifestations and findings from chest radiographs. Ultrasonography has recently been applied to the detection of pulmonary diseases. However, few data have been published showing its effectiveness in detecting pneumonia in children. The objective of this study was to determine the power of lung ultrasonography (LUS) for the diagnosis of pneumonia in children., Methods: This retrospective study was carried out by reviewing medical records. Patients admitted to a pediatric ward with a diagnosis of pneumonia from June 1, 2010 to December 31, 2012 were enrolled in this study. Personal information, laboratory data, characteristics on LUS scan, and the results of chest radiography and LUS were collected. We compared the detection rate of pneumonia by chest radiography and LUS. LUS scans were followed up in 23 patients during the progression of their disease., Results: A total of 163 patients was enrolled. Chest radiography was able to detect pneumonia in 152 patients, whereas LUS detected pneumonia in 159 patients. In LUS, the positive rates of the comet-tail sign, air bronchograms, fluid bronchograms, vascular pattern within the consolidation, and pleural effusion were 50.9%, 93.7%, 20.1%, and 28.9%, respectively. During follow up, the average size of the pneumonia patch in 23 patients decreased from 10.9 ± 8.7 cm(2) to 5.5 ± 8.2 cm(2), and finally to 2 ± 1.9 cm(2) on Day 1, Days 3-5 and Days 7-14, respectively., Conclusion: LUS is a sensitive diagnostic tool with which to identify pneumonia in children. It is also useful in following up the progress of pneumonia. We suggest that LUS is a complementary tool to chest radiography in the diagnosis of pneumonia in children and that the follow up of pneumonia by LUS can reduce the exposure of children to ionizing radiation., (Copyright © 2014. Published by Elsevier B.V.)

It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P < 0.05), improved myocardial dysfunction (left ventricular systolic pressure: 33%; max dP/dt: 20%; min dP/dt: 33%, P < 0.05), and prevented hepatic dysfunction (glutamic-oxaloacetic transaminase: 81 vs. 593 IU/L; glutamic-pyruvic transaminase: 15 vs. 136 IU/L, P < 0.05) compared with LPS-treated rats at 4 h. Heat shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P < 0.05) and elevated lactate dehydrogenase (1,312 vs. 6,301 IU/L, P < 0.05). Furthermore, HSC70 decreased LPS-induced elevation of circulating tumor necrosis factor α and nitrite/nitrate, and tissue expression of inducible nitric oxide synthase, cyclooxygenase 2, and matrix metalloproteinase 9 in the heart and liver. To investigate underlying mechanisms, we found that HSC70 attenuated LPS-induced nuclear translocation of nuclear factor κB subunit p65 by blocking the phosphorylation of inhibitor of nuclear factor κB. Finally, we showed that HSC70 repressed the activation of MAPKs caused by LPS. These results demonstrate that in LPS-induced septic shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor α, nitric oxide, cyclooxygenase 2, and matrix metalloproteinase 9, through mitogen-activated protein kinase/nuclear factor κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.

The authors present a case of citrullinemia with a genotype of argininosuccinate synthetase (ASS1), c.380 G>A (p.R127Q)/c.380 G>A (p.R127Q), in two alleles. A 3-day-old female infant presented with status epilepticus and coma. Laboratory data showed hyperammonemia and marked lactic acidosis in the blood and cerebrospinal fluid; electroencephalography showed severely suppressed cerebral activity and focal paroxysmal volleys of slow and sharp waves (< 1Hz) over the left hemisphere. Real-time transcranial Doppler ultrasonography showed a brain edema and high peaked systolic and low diastolic flows in basal, anterior, and middle cerebral arteries; however, immediately after a blood exchange transfusion, systolic flows were lower and diastolic flows were higher. The resistance indices were significantly different (means: 0.58 vs. 0.37; p=0.01). The patient was placed on diet therapy. After six blood exchange transfusions and peritoneal dialysis, her neurologic examination results and serum ammonia and lactate values were normal. The authors found that electroencephalography and transcranial Doppler ultrasonography were useful for the diagnosis and follow-up treatment of neonatal citrullinemia., (Copyright © 2012. Published by Elsevier B.V.)

This paper proposes a newly developed optical design and an active compensation method for a Blu-ray pickup head system with a liquid crystal (LC) element. Different from traditional pickup lens design, this new optical design delivers performance as good as the conventional one but has more room for tolerance control, which plays a role in antishaking devices, such as portable Blu-ray players. A hole-pattern electrode and LC optics with external voltage input were employed to generate a symmetric nonuniform electrical field in the LC layer that directs LC molecules into the appropriate gradient refractive index distribution, resulting in the convergence or divergence of specific light beams. LC optics deliver fast and, most importantly, active compensation through optical design when errors occur. Simulations and tolerance analysis were conducted using Code V software, including various tolerance analyses, such as defocus, tilt, and decenter, and their related compensations. Two distinct Blu-ray pickup head system designs were examined in this study. In traditional Blu-ray pickup head system designs, the aperture stop is always set on objective lenses. In the study, the aperture stop is on the LC lens as a newly developed lens. The results revealed that an optical design with aperture stop set on the LC lens as an active compensation device successfully eliminated up to 57% of coma aberration compared with traditional optical designs so that this pickup head lens design will have more space for tolerance control.

The aim of this study was to identify the health hazards and possible exposure surveillance markers of workers exposed to nanoparticles during manufacturing and application in comparison to a group of unexposed workers. For this longitudinal study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial-handling workers and 77 unexposed workers were monitored 6 months later. We investigated pulmonary and cardiovascular disease markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were significantly associated with nanomaterial-handling during the 6-month follow-up period. In addition, the small airway damage marker (Clara cell protein 16) and lung function test parameters were also significantly associated with handling nanomaterials. The study markers and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.

Pulmonary vascular remodeling, characterized by disordered proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a pathognomonic feature of pulmonary arterial hypertension. Thus, pharmacologic strategy targeting on anti-proliferation and anti-migration of PASMCs may have therapeutic implications for PAH. Here we investigated the effects and underlying mechanisms of B-type natriuretic peptide (BNP) on angiotensin II (Ang II)-induced proliferation and migration of PASMCs. Proliferation and migration of PASMCs cultured from Wistar rats were induced by Ang II, with or without BNP treatment. In addition, potential underlying mechanisms including cell cycle progression, Ca(2+) overload, reactive oxygen species (ROS) production, signal transduction of MAPK and Akt, and the cGMP/PKG pathway were examined. We found that BNP inhibited Ang II-induced PASMCs proliferation and migration dose dependently. BNP could also arrest the cell cycle progression in the G0/G1-phase. In addition, BNP attenuated intracellular calcium overload caused by Ang II. Moreover, Ang II-induced ROS production was mitigated by BNP, with associated down-regulation of NAD(P)H oxidase 1 (Nox1) and reduced mitochondrial ROS production. Finally, Ang II-activated MAPKs and Akt were also counteracted by BNP. Of note, all these effects of BNP were abolished by a PKG inhibitor (Rp-8-Br-PET-cGMPS). In conclusion, BNP inhibits Ang II-induced PASMCs proliferation and migration. These effects are potentially mediated by decreased calcium influx, reduced ROS production by Nox1 and mitochondria, and down-regulation of MAPK and Akt signal transduction, through the cGMP/PKG pathway. Therefore, this study implicates that BNP may have a therapeutic role in pulmonary vascular remodeling., (© 2013 Wiley Periodicals, Inc.)

Background: Lysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes., Methods: Cell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay., Results: We found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein., Conclusions: Baicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.

Objective: The study objective was to determine the association between preoperative B-type natriuretic peptide levels and outcome after total cavopulmonary connection. Surgical palliation of univentricular cardiac defects requires a series of staged operations, ending in a total cavopulmonary connection. Although outcomes have improved, there remains an unpredictable risk of early total cavopulmonary connection takedown. The prediction of adverse postoperative outcomes is imprecise, despite an extensive preoperative evaluation., Methods: We prospectively enrolled 50 patients undergoing total cavopulmonary connection. We collected preoperative clinical data, preoperative plasma B-type natriuretic peptide levels, and postoperative outcomes, including the incidence of an adverse outcome within 1 year of surgery (defined as death, total cavopulmonary connection takedown, or the need for cardiac transplantation)., Results: The mean age of patients was 4.7 years (standard deviation, 2.1 years). The median (interquartile range) preoperative B-type natriuretic peptide levels were higher in patients who required total cavopulmonary connection takedown and early postoperative mechanical cardiac support (n = 3; median, 55; interquartile range, 42-121) compared with those with a good outcome (n = 47; median, 11; interquartile range, 5-17) (P < .05). A preoperative B-type natriuretic peptide level of 40 pg/mL or greater was highly associated with the need for total cavopulmonary connection takedown (sensitivity, 100%; specificity, 93%; P < .05), yielding a positive predictive value of 50% and a negative predictive value of 100%. Higher preoperative B-type natriuretic peptide levels also were associated with longer intensive care unit length of stay, longer hospital length of stay, and increased incidence of low cardiac output syndrome (P < .05)., Conclusions: Preoperative B-type natriuretic peptide blood levels are uniquely associated with the need for mechanical support early after total cavopulmonary connection and total cavopulmonary connection takedown, and thus may provide important information in addition to the standard preoperative assessment., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

In the exposure process of photolithography, a free-form lens is designed and fabricated for UV-LED (Ultraviolet Light-Emitting Diode). Thin film metallic glasses (TFMG) are adopted as UV reflection layers to enhance the irradiance and uniformity. The Polydimethylsiloxane (PDMS) with high transmittance is used as the lens material. The 3-D fast printing is attempted to make the mold of the lens. The results show that the average irradiance can be enhanced by 6.5~6.7%, and high uniformity of 85~86% can be obtained. Exposure on commercial thick photoresist using this UV-LED system shows 3~5% dimensional deviation, lower than the 6~8% deviation for commercial mercury lamp system. This current system shows promising potential to replace the conventional mercury exposure systems.

Objectives: The present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in-exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD)., Methods: A prospective study was conducted in the pediatric intensive care unit. Children with NMD and ARF treated by combined NIV and MIE were included. Treatment success was defined as freedom from tracheal intubation during the hospital stay. Physiologic indices including PaO2 , PaCO2 , pH, and PaO2 /FiO2 were recorded before and 12, 24 hr after the use of NIV/MIE., Results: Combined NIV/MIE was used in 15 NMD children (mean: 8.1 years, range: 3 months to 18 years) with 16 cases of ARF. There was no mortality in this cohort. Treatment success was achieved in 12 cases (75%), including six cases (38%) demanding "Do Not Intubate." ARF was due to pneumonia, with a mean baseline PaCO2 of 73.2 ± 19.0 mmHg. In the success group, hypercarbia and acidosis improved after use of NIV/MIE for 24 hr (PaCO2 : 71.7 ± 18.6 mmHg vs. 55.8 ± 11.6 mmHg, P < 0.01; pH: 7.29 ± 0.07 vs. 7.38 ± 0.05, P < 0.01). All patients tolerated NIV/MIE well despite transient skin pressure sores in five cases., Conclusions: Combined NIV/MIE is a safe and effective approach to rapidly improve physiologic indices and decrease the need for intubation in NMD children with ARF. NIV/MIE provides a good alternative for those refusing intubation., (© 2013 Wiley Periodicals, Inc.)

Ultrathin percolated high-Ku magnetic films with thicknesses of 2 nm are realized simply by using sputter deposition and post annealing. L1₁ CoPt:MgO, with Ku on the order of 10(7) erg cm(-3), was deposited on a MgO(111) substrate at 350 °C, followed by post annealing to induce complete segregation of the added MgO dopants. The optimized film shows significant enhancement of the out-of-plane coercivity, approximately an order of magnitude greater than that of the CoPt binary film, a remanence ratio close to unity, considerably reduced in-plane magnetization, sharp perpendicular magnetic reversal, and reduced surface roughness in the range of a few angstroms. Microstructure results indicate that MgO precipitates into grains within the interconnected L1₁ grains after appropriate post annealing. The MgO grains, with sizes in the range 2-7 nm, form coherent interfaces to the CoPt matrix and penetrate through the whole depth of the film. The development of ideal non-magnetic domain wall pinning sites explains the optimization of the perpendicular magnetic properties. The advantages of a simple fabrication process, a thin film layer structure, and remarkable enhancement of the magnetic characteristics demanded by ultrahigh-density recording reveal its potential for practical applications.

Objective: To investigate the prevalence and incidence of chronic liver disease in patients with schizophrenia in Taiwan., Methods: We used a random sample of 661,266 subjects aged ≥ 18 from the National Health Research Institute database in the year 2000. Subjects with at least one primary diagnosis of schizophrenia (The International Classification of Diseases, Ninth Revision, Clinical Modification: 295) in 2000 were selected. Patients with a primary or secondary diagnosis of chronic liver disease (The International Classification of Diseases, Ninth Revision, Clinical Modification: 571) were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with schizophrenia and the general population in 2000. We also compared the incidence of chronic liver disease in patients with schizophrenia and the general population from 2001 through 2010., Results: The prevalence of chronic liver disease in patients with schizophrenia (7.0%) was 1.27 times as high as that of the general population (6.1%) in 2000. The average annual incidence of chronic liver disease in patients with schizophrenia from 2001-2010 was also higher than that of the general population (2.9% vs 2.5%, risk ratio, 1.15; 95% confidence interval, 1.07-1.24). Younger patients with schizophrenia were found to have a much higher prevalence and incidence than those in the general population, and diabetes was a risk factor for patients with schizophrenia in developing chronic liver disease., Conclusions: Patients with schizophrenia exhibited a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with schizophrenia have a much higher prevalence and incidence than those in the general population. Co-morbidity with diabetes was the primary risk factor for patients with schizophrenia to develop chronic liver disease., (© 2014 Published by Academy of Psychosomatic Medicine on behalf of Academy of Psychosomatic Medicine.)

Introduction: This study aimed to examine the prevalence rates of both post-traumatic stress disorder (PTSD) and major depression at 12 months in workers experiencing different types of occupational injury in Taiwan. Demographic and injury-related risk factors for psychological symptoms were also evaluated., Methods: Our study candidates were injured workers in Taiwan who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance program. A two-staged survey study was conducted. A self-reported questionnaire including the Brief Symptom Rating Scale and Post-traumatic Symptom Checklist was sent to workers at 12 months after injury. Those who met the criteria were recruited for the second-stage phone interview with a psychiatrist using the Mini-international Neuropsychiatric Interview (MINI)., Results: A total of 1,233 workers completed the questionnaire (response rate 28.0 %). Among them, 167 (13.5 %) fulfilled the criteria for the MINI interview and were invited. A total of 106 (63.5 %) completed the phone interview. The estimated rate of either PTSD/PPTSD or major depression was 5.2 %. The risk factors for psychological symptoms were female gender, lower education level, loss of consciousness after occupational injury, injury affecting physical appearance, occupational injury experience before this event, life experience before and after this injury, length of hospital stay, self-rated injury severity, and percentage of income to the family., Conclusions: These results showed that occupational injury can cause long-term psychological impact in workers. Key demographic and injury characteristics may enhance the identification of at-risk occupational injured workers who would benefit from targeted screening and early intervention efforts.

Viral replication depends on host proteins to supply energy and replication accessories for the sufficient production of viral progeny. In this study, we identified fructose-bisphosphate aldolase A as a binding partner of Japanese encephalitis virus (JEV) untranslated regions (UTRs) on the antigenome via RNA affinity capture and mass spectrometry. Direct interaction of aldolase A with JEV RNAs was confirmed by gel mobility shift assay and colocalization with active replication of double-stranded RNA in JEV-infected cells. Infection of JEV caused an increase in aldolase A expression of up to 33%. Knocking down aldolase A reduced viral translation, genome replication, and viral production significantly. Furthermore, JEV infection consumed 50% of cellular ATP, and the ATP level decreased by 70% in the aldolase A-knockdown cells. Overexpression of aldolase A in aldolase A-knockdown cells increased ATP levels significantly. Taken together, these results indicate that JEV replication requires aldolase A and consumes ATP. This is the first report of direct involvement of a host metabolic enzyme, aldolase A protein, in JEV replication., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recent studies point to a pivotal role of Polycomb repressive complex 2 (PRC2) in stem cell function and cancer. Loss-of-function approaches targeting individual PRC2 subunits have, however, generated findings that are difficult to reconcile. Here, we prevent assembly of both Ezh1- and Ezh2-containing PRC2 complexes by conditional deletion of Eed, a core subunit, and assess hematopoiesis. We find that deletion of Eed exhausts adult bone marrow hematopoietic stem cells (HSCs), although fetal liver HSCs are produced in normal numbers. Eed-null neonatal HSCs express HSC signature genes but are defective in maintenance and differentiation. Comparative gene expression profiling revealed that neonatal and adult HSCs lacking Eed upregulated gene sets of conflicting pathways. Deletion of Cdkn2a, a PRC2 target gene, in Eed-null mice enhances hematopoietic stem/progenitor cell (HSPC) survival but fails to restore HSC functions. Taken together, our findings define developmental-stage-specific requirements for canonical PRC2 complexes in normal HSC function., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.

This work explores the possibility of increasing the density of negatively charged nitrogen-vacancy centers ([NV(-)]) in nanodiamonds using nitrogen-rich type Ib diamond powders as the starting material. The nanodiamonds (10-100 nm in diameter) were prepared by ball milling of microdiamonds, in which the density of neutral and atomically dispersed nitrogen atoms ([N(0)]) was measured by diffuse reflectance infrared Fourier transform spectroscopy. A systematic measurement of the fluorescence intensities and lifetimes of the crushed monocrystalline diamonds as a function of [N(0)] indicated that [NV(-)] increases nearly linearly with [N(0)] at 100-200 ppm. The trend, however, failed to continue for nanodiamonds with higher [N(0)] (up to 390 ppm) but poorer crystallinity. We attribute the result to a combined effect of fluorescence quenching as well as the lower conversion efficiency of vacancies to NV(-) due to the presence of more impurities and defects in these as-grown diamond crystallites. The principles and practice of fabricating brighter and smaller fluorescent nanodiamonds are discussed.

Background: KMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE) 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.7 cells and bone loss induced by ovariectomy in mice, and the underlying mechanisms., Principal Findings: In vitro, KMUP-1 inhibited RANKL-induced TRAP activity, the formation of multinucleated osteoclasts and resorption-pit formation. It also inhibited key mediators of osteoclastogenesis including IL-1β, IL-6, TNF-α and HMGB1. In addition, KMUP-1 inhibited RANKL-induced activation of signaling molecules (Akt, MAPKs, calcium and NF-κB), mRNA expression of osteoclastogensis-associated genes (TRAP, MMP-9, Fra-1, and cathepsin K) and transcription factors (c-Fos and NFATc1). Furthermore, most inhibitory effects of KMUP-1 on RANKL-mediated signal activations were reversed by a protein kinase A inhibitor (H89) and a protein kinase G inhibitor (KT5823). In vivo, KMUP-1 prevented loss of bone mineral content, preserved serum alkaline phosphate and reduced serum osteocalcin in ovariectomized mice., Conclusions: KMUP-1 inhibits RANKL-induced osteoclastogenesis in vitro and protects against ovariectomy-induced bone loss in vivo. These effects are mediated, at least in part, by cAMP and cGMP pathways. Therefore, KMUP-1 may have a role in pharmacologic therapy of osteoporosis.

Objective: We investigated the prevalence and incidence of chronic obstructive pulmonary disease (COPD) among patients with schizophrenia in Taiwan., Methods: From the database provided by the National Health Research Institute, we obtained a random sample of 766,427 subjects aged ≥18 years in 2005. Subjects with a primary or secondary diagnosis of COPD during 2005 were identified. We compared the prevalence of COPD in schizophrenic patients with that in the general population. We also detected new cases of COPD from 2006 to 2008., Results: The prevalence of COPD in patients with schizophrenia was higher than that in the general population (3.83% vs. 2.88%, odds ratio [OR] 1.66; 95% confidence interval [CI]),1.42-1.94) in 2005. Compared with the general population, patients with schizophrenia had a higher prevalence of COPD in individuals <50 years old and ≥70 years old; among both sexes, and among insurance amount of a fixed premium and an amount less than US$640. Patients with schizophrenia had a higher annual incidence of COPD than that in the general population (2.21% vs. 1.43%, risk ratio 1.83; 95% CI, 1.62-2.07). The higher incidence of COPD in patients with schizophrenia was associated with increased age and male sex., Conclusions: Patients with schizophrenia had a higher prevalence and incidence of COPD than individuals in the general population in Taiwan. Younger adults and men with schizophrenia had a much higher prevalence of COPD compared with those groups in the general population, a result deserving further study., (Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Shipbreaking workers are typically exposed to a wide range of hazardous chemicals. However, long-term follow-up studies of their mortality patterns are lacking. This study examined mortality among shipbreaking workers over a 24-year follow-up period., Methods: A total of 4,962 shipbreaking workers were recruited from the database of the Kaohsiung Shipbreaking Workers Union. The data were then linked to the Taiwan National Death Registry from 1985 to 2008. The mortality ratios-standardized for age and calendar years-(SMRs) for various causes of deaths were calculated with reference to the general population of Taiwan., Results: Among men workers, a statistically significant increased SMR was observed for all causes (SMR = 1.28), all cancers (SMR = 1.26; particularly noteworthy for lesions of oral and nasopharyngeal: SMR 2.03, liver: SMR 4.63, and lung: SMR 1.36), cirrhosis of the liver (SMR = 1.32), and accidents (SMR = 1.91). A statistically significant increase in mortality was observed for respiratory system cancer (SMR = 1.87) and lung cancer (SMR = 1.91) among workers with a longer duration of employment (≥7 years). The result also showed that among shipbreaking workers who were still alive, two people had mesothelioma and 10 people have asbestosis., Conclusions: Those employed in shipbreaking industries experienced an increase in mortality from all causes. The increased SMR for lung cancer was probably related to asbestos, metals, and welding fume exposure., (Copyright © 2013 Wiley Periodicals, Inc.)

Study Objective: Automated external defibrillator use by lay bystanders during out-of-hospital cardiac arrest rarely occurs but can improve survival. We seek to estimate risk for out-of-hospital cardiac arrest by location type and evaluate current automated external defibrillator deployment in a Canadian urban setting to guide future automated external defibrillator deployment., Methods: This was a retrospective analysis of a population-based out-of-hospital cardiac arrest database. We included consecutive public location, nontraumatic, out-of-hospital cardiac arrests occurring in Toronto from January 1, 2006, to June 30, 2010, captured in the Resuscitation Outcomes Consortium Epistry database. Two investigators independently categorized each out-of-hospital cardiac arrest and automated external defibrillator location into one of 38 categories. Total site counts in each location category were used to estimate average annual per-site cardiac arrest incidence and determine the relative automated external defibrillator coverage for each location type., Results: There were 608 eligible out-of-hospital cardiac arrest cases. The top 5 location categories by average annual out-of-hospital cardiac arrests per site were race track/casino (0.67; 95% confidence interval [CI] 0 to 1.63), jail (0.62; 95% CI 0.3 to 1.06), hotel/motel (0.15; 95% CI 0.12 to 0.18), hostel/shelter (0.14; 95% CI 0.067 to 0.19), and convention center (0.11; 95% CI 0 to 0.43). Although schools were relatively lower risk for cardiac arrest, they represented 72.5% of automated external defibrillator-covered locations in the study region. Some higher-risk location types such as hotel/motel, hostel/shelter, and rail station were severely underrepresented with respect to automated external defibrillator coverage., Conclusion: We have identified types of locations with higher per-site risk for cardiac arrest relative to others. We have also identified potential mismatches between cardiac arrest risk by location type and registered automated external defibrillator distribution in a Canadian urban setting., (Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Objective: B-type natriuretic peptide is used in the diagnosis, risk stratification, and management of adult patients with cardiac disease. However, its use in infants with congenital heart disease has been limited, particularly in the perioperative period. Our objective was to determine the alterations in perioperative B-type natriuretic peptide levels and their predictive value on postoperative outcomes, in infants undergoing congenital heart surgery., Methods: We prospectively enrolled 115 patients: 24 with univentricular heart disease undergoing a modified Norwood procedure, 11 with d-transposition of the great arteries, 55 with hemodynamically important left-to-right shunt, and 25 with tetralogy of Fallot undergoing primary repair. Clinical data and B-type natriuretic peptide samples were collected before and 2, 12, and 24 hours after cardiopulmonary bypass. Univariate analysis and multivariate linear regression analysis were performed., Results: The perioperative B-type natriuretic peptide levels were lesion specific. Patients with d-transposition of the great arteries and univentricular heart disease had high preoperative B-type natriuretic peptide levels that decreased postoperatively, and those with hemodynamically important left-to-right shunts and tetralogy of Fallot had lower preoperative levels that increased during the first 12 hours postoperatively. The patients with univentricular heart disease with an adverse outcome had a significantly greater 24-hour B-type natriuretic peptide level than those without (P < .05). Those with hemodynamically important left to right shunts and an adverse outcome had a greater 12-hour B-type natriuretic peptide level than those without (P < .05). A 12-hour postoperative/preoperative ratio greater than 45 was 100% sensitive and 82% specific for an adverse outcome in the patients with tetralogy of Fallot., Conclusions: The perioperative changes in B-type natriuretic peptide levels and their ability to predict outcomes are lesion-specific. Characterization of these changes might be useful in caring for infants after congenital heart surgery., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype-phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10-13kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10-11kb, with normal length being 50-300kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: This study aimed to investigate the impact of psychological symptoms on return to work (RTW) in workers after occupational injuries., Methods: Our study candidates were injured workers who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance. A self-reported questionnaire including Brief Symptom Rating Scale (BSRS-50) and RTW was sent to workers at 12 weeks after injury. At 1 year, all participants were contacted again to determine whether or not they had RTW., Results: A total of 2001 workers completed the questionnaire (response rate 45.5 %) at 12 weeks after injury, among them, 1,149 had returned to work. Among the 852 who were unable to return to work at 12 weeks after injury, 225 reportedly returned to work by 1 year. A proportional hazards regression indicated that after adjusting for all possible risk factors, higher scores in BSRS-50 and BSRS-5 at 12 weeks after injury were significant risk factors for not return to work (NRTW) at 1 year after injury. Other risk factors were gender, education level, length of hospitalization, affected physical appearance, and injury type. Among 10 psycho-physiological symptoms of BSRS-50, a proportional hazards regression indicated that high score in phobic-anxiety scale was a risk factor for NRTW., Conclusions: After considering all other factors, psychological symptoms further predicted poorer probability of returning to work after occupational injury, and phobic-anxiety was the most significant symptom predicting poor RTW. Development of preventive measures among injured workers according to the risk factors identified in this study is warranted.

Many human tumors show significant changes in their signal transduction pathways and, thus, the way the cells interact with their environment. Often caused by chromosomal rearrangements, including gene amplifications, translocations or deletions, the altered levels of gene expression may provide a tumor-specific signature that can be exploited for diagnostic or therapeutic purposes. We investigated the utility of multiplexed fluorescence in situ hybridization (FISH) using non-isotopically labeled cDNA probes detected by Spectral Imaging as a sensitive and rapid procedure to measure tumor-specific gene expression signatures. We used a commercially available system to acquire and analyze multicolor FISH images. Initial investigations used panels of fluorescent calibration standards to evaluate the system. These experiments were followed by hybridization of five-to-six differently labeled cDNA probes, which target the transcripts of tyrosine kinase genes known to be differently expressed in normal cells and tumors of the breast or thyroid gland. The relatively simple, yet efficient, molecular cytogenetic method presented here may find many applications in characterization of solid tumors or disseminated tumor cells. Addressing tumor heterogeneity by means of multi-parameter single cell analyses is expected to enable a wide range of investigations in the areas of tumor stem cells, tumor clonality and disease progression.

Objective: Inflammation is an important molecular basis of atherosclerosis. Recent studies have shown that dihydropyridine calcium channel blockers (CCBs) can exert potent anti-inflammatory effects in models of vascular dysfunction. The purpose of the present study was to evaluate anti-inflammatory effects and mechanisms of lercanidipine and labedipinedilol-A, new generation dihydropyridine CCBs, in rat vascular smooth muscle cells (VSMCs) exposed to lipopolysaccharide (LPS) and interferon-γ (IFN-γ)., Methods and Results: MTT, Griess reagent, RT-PCR, ELISA, gelatin zymography, immunocytochemistry and Western blotting were employed. We found that lercanidipine and labedipinedilol-A attenuated production of NO, ROS and TNF-α from LPS/IFN-γ-stimulated VSMCs. In addition, they both diminished the LPS/IFN-γ-induced expression of iNOS protein and mRNA, with attenuation of HMGB1 cytosolic translocation and subsequent extracellular release. Furthermore, they down-regulated MMP-2/MMP-9 activities, whereas expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9, was up-regulated. Finally, we found that lercanidipine and labedipinedilol-A inhibited the nuclear translocation of NF-κB and suppressed the phosphorylation of JNK, p38 MAPK and Akt., Conclusion: Lercanidipine and labedipinedilol-A can exert their anti-inflammatory effects through suppression of NO, ROS and TNF-α through down-regulation of iNOS, MMP-2/MMP-9, and HMGB1, with inhibition of signaling transduction of MAPKs, Akt/IkB-α and NF-κB pathways. These findings implicate a valuable role of new generation dihydropyridine CCBs lercanidipine and labedipinedilol-A for the treatment of inflammatory vascular diseases., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect., Methods: An aorta-to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR-γ agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk. Lung tissue from five normal 4-wk-old lambs was used for comparisons., Results: At 4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled nitric oxide (NO) in RG- and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated, shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177 eNOS protein, and eNOS activity were increased, and NADPH activity, rac1, superoxide levels, and 3-NT levels were decreased, as compared with vehicle-treated shunt lambs. PPAR-γ protein expression was lower in vehicle-treated shunt lambs than in normal and RG-treated shunt lambs., Conclusion: The PPAR-γ agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.

Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present bottlenecks in the procedure are a limited number of commercial, non-isotopically labeled probes that can be combined in multiplex FISH assays and the relatively high price and effort to develop additional probes. We describe a streamlined approach for rapid probe definition, synthesis and validation, which is based on the analysis of publicly available DNA sequence information, also known as "database mining". Examples of probe preparation for the human gonosomes and chromosome 16 as a selected autosome outline the probe selection strategy, define a timeline for expedited probe production and compare this novel selection strategy to more conventional probe cloning protocols.