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In October 2012, a maternal pertussis vaccination programme was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the programme by comparing pertussis-related infant hospitalisations and deaths in 2012-2017 with non-vaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the programme.

Ho-Jun Seo,1 Young Hee Choi,2 Yong-An Chung,3 Wangku Rho,1 Jeong-Ho Chae11Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Metta Institute of Cognitive Behavior Therapy, Seoul, South Korea; 3Department of Radiology, Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaAim: Inconsistent results continue to be reported in studies that examine the neural correlates of cognitive behavioral therapy (CBT) in patients with panic disorder. We examined the changes in regional cerebral blood flow (rCBF) associated with the alleviation of anxiety by CBT in panic patients.Methods: The change in rCBF and clinical symptoms before and after CBT were assessed using single photon emission computed tomography and various clinical measures were analyzed.Results: Fourteen subjects who completed CBT showed significant improvements in symptoms on clinical measures, including the Panic and Agoraphobic Scale and the Anxiety Sensitivity Index-Revised. After CBT, increased rCBF was detected in the left postcentral gyrus (BA 43), left precentral gyrus (BA 4), and left inferior frontal gyrus (BA 9 and BA 47), whereas decreased rCBF was detected in the left pons. Correlation analysis of the association between the changes in rCBF and changes in each clinical measure did not show significant results.Conclusion: We found changes in the rCBF associated with the successful completion of CBT. The present findings may help clarify the effects of CBT on changes in brain activity in panic disorder.Keyword: single photon emission computed tomography (SPECT), anxiety, neural correlate, brain activity

A 1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (HAT-CN)/Ag/HAT-CN transparent electrode for organic light-emitting devices (OLEDs) was investigated. The current density of OLEDs was enhanced with an increase in the Ag layer thickness of a HAT-CN/Ag/HAT-CN anode. While the luminance of the OLEDs with a HAT-CN/Ag/HAT-CN anode slightly decreased with increasing thickness of the upper HAT-CN layer, the current efficiency of the OLEDs with thicknesses for the Ag layer of 20 nm and for the upper HAT-CN layer of 100 nm was almost two times higher than that of OLEDs with an ITO anode. Electroluminescence spectra of the OLEDs with a HAT-CN/Ag/HAT-CN anode were shifted due to the micro-cavity effect in the stacked anode, which was confirmed by the transmittance spectra.

Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time.

For evaluating the effect of light absorption in vertically structured thin film light-emitting diodes (VLEDs), we investigate the dependence of the efficiencies on the several specific parameters including thickness and doping concentration (N(D)) of the n-GaN layer, a design of hetero-structures of the n-GaN layer, and a number of pairs of multi-quantum wells (MQWs). Generally, there is a complementary relation between internal quantum efficiency (IQE) and light extraction efficiency (LEE). However, we confirmed that LEE determined by light absorption is more dominant than IQE in VLED structures with a textured surface, from numerical simulation and experimental results. Effect of light absorption is more prominent in the vertical chip with a textured surface than in that with a flat surface, because a travel length of light extracted from the textured surface is longer. Minimizing light absorption in VLEDs is a key technology for improving light output, and light absorption speaks for the index of enhancement by the general technologies for improving LEE.

Purpose For treatment of univentricular heart, the Fontan operation has been established as the definitive palliation. The current controversy is mainly based on the high incidence of arrhythmias after an intra-atrial lateral tunnel Fontan operation. Methods From January 1995 until April 2002. 46 children underwent a Fontan-type operation with or without a small fenestration. In 33 patients (group I) an Intracardiac tunnel and in 13 patients (group II) an extracardiac conduit procedure was performed. Principal findings There was no perioperative mortality. All patients showed postoperative a significant increase of arterial oxygen saturation, from 76 to 86% after surgery with fenestration, or to 90.5% without fenestration respectively. In patients with fenestration procedure, the saturation rose to 90% after closure of fenestrations 9 to 12 months after operation. Conclusions Modified Fontan operations can be performed in normothermia on the beating heart with acceptable mortality. The extracardiac conduit Fontan procedure has the benefits of less surgical injury and a higher intraoperative flexibility.

A congenital aneurysm of the ductus arteriosus Botalli was detected by chest X-ray as an intrathoracic mass in a 7-day-old infant. Following confirmation of the diagnosis by echocardiography and MRI the aneurysm was successfully resected via left lateral thoracotomy without cardiopulmonary bypass. The postoperative course was uneventful. Six years after operation the patient is asymptomatic and growing normally. An intrathoracic mass may be considered in the differential diagnosis especially in infants and children. Aneurysms of ductus arteriosus potentially are associated with serious complications. Timely diagnosis and early surgical intervention are decisive for prevention of serious complication and death.

Purpose: To determine whether the methanol extract of Polyopes affinis (MEPA) down-regulates the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.Methods: The production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reagents and enzyme-linked immunosorbent assay (ELISA), respectively. Expression levels of mRNA and protein in LPS-stimulated BV2 microglial cells were assessed by reverse transcription-polymerase (RT-PCR) and Western blot analysis. Activation of nuclear factor-êB (NF-êB) was detected by electrophoretic mobility shift assay (EMSA).Results: MEPA inhibited the expression of LPS-induced pro-inflammatory mediators, NO and PGE2, as well as their respective genes, iNOS and COX-2, at both protein and mRNA levels, without any accompanying cytotoxicity. Moreover, treatment with MEPA significantly suppressed the LPS-induced DNA-binding activity of NF-êB, which is known as a main transcription factor for the regulation of proinflammatory genes, as well as the nuclear translocation of its subunit p65 and p50, by degrading IêBá.MEPA increased Akt dephosphorylation which leads to suppression of the DNA-binding activity of NF-kB in LPS-stimulated BV2 microglial cells and suppressed phosphorylation of ERK and JNK, which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway for regulating proinflammatory genes.Conclusion: Our results indicate that MEPA down-regulates pro-inflammatory mediators such as NO and PGE2 by suppressing Akt-dependent NF-êB activity as well as phosphorylation of ERK and JNK inLPS-stimulated BV2 microglial cells.Keywords: Polyopes affinis, Nitric oxide, Prostaglandin E2, Nuclear factor-kB

Purpose: To investigate the effects of the methanol extract of Polyopes lancifolius (MEPL) on the expression of matrix metalloproteinase-9 (MMP-9) and invasion in T24 human bladder carcinoma cells.Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses were performed to assess the expression of MMP-9 and its regulatory proteins. MMP-9 activity was evaluated using zymography while matrigel infiltration was performed to assess T24 bladder carcinoma invasion. Electrophoretic mobility assay was used to investigate the nuclear factor-κB (NF-κB) activity.Results: The expression and activity of MMP-9 were significantly increased in response to TNF-α, but MEPL suppressed TNF-α-induced MMP-9 expression and activity. MEPL also inhibited TNF-α-induced MMP-9 expression at the transcriptional level by blocking the activation of the NF-κB signaling pathway. Furthermore, the extract suppressed TNF-α-induced phosphorylation of IκBα and consequently sustained cytosolic p65 and p50 expression. Matrigel invasion assay showed that MEPL significantly reduced TNF-α-induced invasion of T24 bladder carcinoma cells.Conclusion: Collectively, these data indicate that MEPL regulates TNF-α-induced MMP-9 expression by suppressing NF-κB activity.

Purpose: To investigate the anti-inflammatory effects of aqueous extract of Orixa japonica (AEOJ) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.Methods: The expression of mRNA and protein using RT-PCR and Western blot analysis was investigated. The level of nitric oxide (NO) production was analyzed using Griess reaction. Release of prostaglandin E2 (PGE2) and tumor necrosis factor- (TNF-) was determined using sandwich ELISA.Results: AEOJ potently inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor- (TNF-) in LPS-stimulated RAW 264.7 cells. Consistent with these findings, AEOJ wasalso found to significantly reduce LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF- at the transcriptional level. Additionally, AEOJ attenuated LPSinducedNF-B activity via the inhibition of IB phosphorylation and degradation. It was also found that the NF-B inhibitor N-acetyl cysteine (NAC) attenuated LPS-induced gene expression of iNOS, COX-2,and TNF-. These results indicate that AEOJ attenuates LPS-induced inflammatory mediators such as NO, PGE2, and TNF- via suppression of NF-B activity.Conclusion: These results suggest that AEOJ has a potential activity to alleviate LPS-induced inflammation.

Fungal infection is prevalent in patients with diabetes mellitus. Thus, we investigated whether a pharmacokinetic interaction occurs between the anti-fungal agent itraconazole and the anti-glycaemic drug metformin, as both drugs are commonly administered together to diabetic patients and are metabolized via hepatic CYP3A subfamily in rats.Itraconazole (20 mg·kg(-1)) and metformin (100 mg·kg(-1)) were simultaneously administered i.v. and p.o. to rats. Concentrations (I) of each drug in the liver and intestine, maximum velocity (V(max)), Michaelis-Menten constant (K(m)) and intrinsic clearance (CL(int) ) for the disappearance of each drug, apparent inhibition constant (K(i) ) and [I]/K(i) ratios of each drug in the liver and intestine were determined. Also the metabolism of each drug in rat and human CYPs was measured in vitro.After simultaneous administration of both drugs, either i.v. or p.o., the total area under the plasma concentration-time curve from time zero to infinity (AUC)s of itraconazole and metformin were significantly greater than that of either drug administered alone. The metabolism of itraconazole and metformin was significantly inhibited by each other via CYP3A1 and 3A2 in rat and 3A4 in human microsomes.The significantly greater AUCs of itraconazole and metformin after i.v. administration of both drugs are probably due to competitive inhibition of the metabolism of each drug by each other via hepatic CYP3A1/2. Whereas after oral administration of both drugs, the significantly greater AUCs of each drug administered together than that of either drug alone is mainly due to competitive inhibition of intestinal metabolism of each drug by each other via intestinal CYP3A1/2.

The aim of this study was to assess the relationship between body fat mass (BFM) and erectile dysfunction (ED) in Korean men. This study was a cross-sectional study using data on 208 men (the mean age=67.4+/-8.2). ED was diagnosed by the International Index of Erectile Function (IIEF)-5 and body fat percentage (BF%) was quantified with bioelectrical impedance. BF% was divided into quintiles (quintile 1:or =20.5%, quintile 2: 20.6-23.2%, quintile 3: 23.3-25.8%, quintile 4: 25.9-28.8%, quintile 5:or =28.9%). Using subjects with quintile 3 of BF% as reference, the adjusted odds ratios of subjects with the lowest quintile of BF% and with the highest quintile were 9.29 (95% CI: 2.29-37.72) and 4.99 (95% CI: 1.37-18.09), respectively. This study showed that BFM and ED had a U-shaped relationship in Korean men. These findings suggest that not only obesity but also a low BFM may be a risk factor of ED in Asians.

We studied the postmortem vascular anatomy of four patients with total anomalous pulmonary venous connection (TAPVC) with obstruction using a silicone rubber casting method. Two patients were studied clinically but died before therapeutic intervention, one died after corrective surgery, and another was not diagnosed before death. The morphologic types were supracardiac (2), infracardiac (1), and mixed (1). One of the supracardiac forms had a stenosis at the left vertical vein by a bronchoarterial vise, and a collateral channel to the right superior caval vein was also present. In the other supracardiac case, a left upper pulmonary vein was connected to the left vertical vein above the stenotic portion, resulting in postoperative pulmonary hemorrhage into the left upper lobe. The patient with infracardiac TAPVC had a tree-shaped descending vertical vein and small opening at the inferior caval vein. In the mixed type, a right upper pulmonary vein ran between the pulmonary artery and bronchus draining into the superior caval vein, and the rest of the drainage was to the portal vein.

Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case-control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.-1289C>T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR)=0.63 (0.48-0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA-protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

BACKGROUND Degeneration remains the major drawback of bioprostheses. Among various concepts to mitigate degeneration, the use of autologous pericardium for intraoperative construction of aortic valves (ATCV) was revived recently. Based on in-vivo studies the problem of tissue failure was claimed to be oversome by short immersion in glutaraldehyde. METHODS Two often ATCV implanted 1994-1996 had to be replaced because of valvular insufficiency due to leaflet shrinkage or tearing. Pathophysiology of failure was evaluated by light microscopy and immune histology, scanning electron microscopy (SEM) and determination of tissue calcium content (AAS). RESULTS AAS revealed high calcium levels in the shrunken and low levels in the torn leaflets. Histology demonstrated extensive fiber degeneration without inflammation in the destructed and moderate degeneration in the intact leaflets. SEM showed smooth surfaces in the 'normal' and exposure of collagen in the degenerated leaflet associated with calcification. Tears occurred close to the stents. CONCLUSIONS Failure of ATCV is characterised by either shrinkage and calcification despite a short tanning or by tearing related to the stent design. Clinical use of ATCV cannot be recommended at present.