Hepatitis B virus infection among pregnant women in Taiwan: Comparison between women born in Taiwan and other southeast countries

<p>Abstract</p> <p>Background</p> <p>Taiwan's national vaccination program has successfully decreased the prevalence of hepatitis B infection after twenty years of implementation and might be indirectly beneficial to the second generation. In this study, we compared the hepatitis B infection status of two groups: pregnant Taiwanese women and other Southeast Asian women, who because they had immigrated later in life to Taiwan by marriage to a Taiwanese man, had not been exposed to that vaccination program to evaluate the effect of hepatitis vaccination program on women of child-bearing age and further explored the potential impact of immigration on the hepatitis B public health policy in Taiwan.</p> <p>Methods</p> <p>Data was collected from 10,327 women born in Taiwan and 1,418 women born in other Southeast Asian countries, both groups receiving prenatal examinations at Fooyin University Hospital between 1996 and 2005. The results of serum hepatitis B s-Antigen (HBsAg) and hepatitis B e-Antigen (HBeAg) tests and other demographic data were obtained by medical chart review.</p> <p>Results</p> <p>The pregnant women from Taiwan had a higher HBsAg positive rate (15.5%) but lower HBeAg(+)/HBsAg(+) ratio (32.1%) than the women from other countries (8.9% and 52.4%). For those born before July, 1984, the period of no national vaccination program, Taiwanese women had a higher HBsAg positive rate than other Southeast Asian women (15.7% vs. 8.4%), but for women born after that day and before June 1986, the period of vaccination for high risk newborns, the HBsAg positive rates found to be slightly lower for Taiwanese women than for other Southeast Asian women (11.4% vs. 12.3%) and the difference was more significant (3.1% vs. 28.6%) after June 1986, the period of vaccination for all newborns. While the HBeAg(+)/HBsAg(+) ratios decreased with age in both groups, they were consistently higher in women from other Southeast Asian countries than in women born in Taiwan after age 20.</p> <p>Conclusion</p> <p>In Taiwan, the neonatal vaccination program that was implemented in 1984 has successfully reduced hepatitis B infection among pregnant women in present day, and is likely to indirectly prevent hepatitis B infection in the next generation. However, the increasing number of pregnant women from other Southeast Asian countries without a national neonatal vaccination program or with a program that was introduced later than the one in Taiwan will likely lessen the positive impact of this program and should be further assessed.</p

Large-scale gene expression analysis of osteoblasts cultured on three different Ti–6Al–4V surface treatments

To improve implant biocompatibility, we developed a simple cost-effective thermal surface treatment allowing an increase in the oxide layer thickness of a titanium (Ti) alloy used in orthopaedic implants. The goal of this study was to test in vitro the reaction of osteoblasts to the developed surface treatment and to compare it to the osteoblast reaction to two other surface treatments currently used in the practice of implant surgery. Quantification of osteoblast gene expression on a large scale was used in this study. The kinetics of gene expression over 120 h was followed for 58 genes to quantify the effect of the developed surface treatment. Twenty eight genes were further selected to compare the effects of surface treatments on osteoblasts. Based on the genes studied, we could propose a general pathway for the cell reaction according to the surface treatments used: (1) metal ion release changes the time course of gene expression in the FAK pathway; (2) once the accumulation of metal ions released from the Ti surface exceeds a threshold value, cell growth is diminished and apoptosis may be activated; (3) PTK up-regulation is also induced by metal ion release; (4) the expression of Bcl-2 family and Bax may suggest that metal ions induce apoptosis. The developed treatment seems to increase the Ti–6Al–4V biocompatibility as highlighted by the lower impact of this treatment by the different pathways studied, on the lower inflammatory reaction that could be induced, as well as by the lower induced osteoblast apoptosis compared to the two other surface treatments

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD

13 páginas, 7 figurasCurrent clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their servicesPeer reviewe

Genetics of Mechanosensation in the Heart

Mechanosensation (the ultimate conversion of a mechanical stimulus into a biochemical signal) as well as mechanotransduction (transmission of mechanically induced signals) belong to the most fundamental processes in biology. These effects, because of their dynamic nature, are particularly important for the cardiovascular system. Therefore, it is not surprising that defects in cardiac mechanosensation, are associated with various types of cardiomyopathy and heart failure. However, our current knowledge regarding the genetic basis of impaired mechanosensation in the cardiovascular system is beginning to shed light on this subject and is at the centre of this brief review

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

An investigation into the surface properties and biological performance of treated Ti-6A1-4V alloy

Previous research has demonstrated the effectiveness of applying a simple ageing treatment over the ASTM standard passivation treatment to reduce metal ion release from Ti-6Al-4V alloy into bovine serum solution. The present study aims to further understand the mechanisms behind the improved dissolution resistance exhibited by the aged Ti-6Al-4V alloy using a number of sophisticated surface analysis techniques, X-ray photoelectron spectroscopy and atomic force microscopy. Furthermore, osteoblastic cell culture and functional genomic studies have been employed to fully characterise the biological performance of the treated implants.This study has demonstrated that the passivation treatment results in the elimination of vanadium from the oxide layers. The O/Ti ratio of the passivated sample significantly changes with immersion time in serum, indicating that further oxidation and dissolution processes were occurring. In contrast, the aged oxide surface is more stable and possesses hydroxylated groups, which are thought to play an important role in the reaction with serum proteins. In addition, this research has observed that the side effects of Al2O3 grit-blasting and heat treatment associated with the hydroxyapatite plasma-spraying coating cause the change in the Al% surface composition and the loss of chemisorbed H2O groups; this in turn, affects the metal ion dissolution behaviour of the treated implant. Furthermore, a potentiodynamic test was used to assess the nature of the passive film; the aged surface showed better dissolution resistance and was less affected by bovine serum solution than other treatments.Based on the findings of this study the aged surface has demonstrated much improved dissolution resistance, which is reflected in its biological performance. Moreover, the genocompatibility test is introduced in this study to complement existing biocompatability tests and to provide further detailed information on cell-implant interface reactions.</p

An investigation into the surface properties and biological performance of treated Ti-6A1-4V alloy

Previous research has demonstrated the effectiveness of applying a simple ageing treatment over the ASTM standard passivation treatment to reduce metal ion release from Ti-6Al-4V alloy into bovine serum solution. The present study aims to further understand the mechanisms behind the improved dissolution resistance exhibited by the aged Ti-6Al-4V alloy using a number of sophisticated surface analysis techniques, X-ray photoelectron spectroscopy and atomic force microscopy. Furthermore, osteoblastic cell culture and functional genomic studies have been employed to fully characterise the biological performance of the treated implants.This study has demonstrated that the passivation treatment results in the elimination of vanadium from the oxide layers. The O/Ti ratio of the passivated sample significantly changes with immersion time in serum, indicating that further oxidation and dissolution processes were occurring. In contrast, the aged oxide surface is more stable and possesses hydroxylated groups, which are thought to play an important role in the reaction with serum proteins. In addition, this research has observed that the side effects of Al2O3 grit-blasting and heat treatment associated with the hydroxyapatite plasma-spraying coating cause the change in the Al% surface composition and the loss of chemisorbed H2O groups; this in turn, affects the metal ion dissolution behaviour of the treated implant. Furthermore, a potentiodynamic test was used to assess the nature of the passive film; the aged surface showed better dissolution resistance and was less affected by bovine serum solution than other treatments.Based on the findings of this study the aged surface has demonstrated much improved dissolution resistance, which is reflected in its biological performance. Moreover, the genocompatibility test is introduced in this study to complement existing biocompatability tests and to provide further detailed information on cell-implant interface reactions.</p