Universal antenatal human immunodeficiency virus testing in Hong Kong: consensus statement.

Following the recommendations of the Advisory Council on AIDS, Hong Kong, the Hospital Authority announced plans to introduce universal antenatal screening for human immunodeficiency virus infection and hence, a consensus conference was held to discuss strategies for implementing such screening in Hong Kong. This paper reports the discussions of the consensus conference. The consensus meeting group consisted of 15 clinicians and scientists from Hong Kong, Macau, and Thailand. Seven commonly asked questions concerning mother-to-child transmission of human immunodeficiency virus were selected for discussion by the participating panellists. Information on the laboratory diagnosis of human immunodeficiency virus infection and the efficacy of preventive measures in reducing mother-to-child transmission of human immunodeficiency virus were reviewed. Data from local studies was also presented and discussed. The timing, potential problems, and cost issues involved in testing all pregnant women in Hong Kong for human immunodeficiency virus were then considered.published_or_final_versio

Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells

The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 mu g intraperitoneally injected in syngeneic mice. Immune deficient mice failed to respond to the peptide protective effect. Rb9 induced increased CD8+ T and low Foxp3+ T cell infiltration in lung metastases and high IFN-gamma and low TGF-beta in lymphoid organs. The peptide co-localized with F-actin and a nuclear site in dendritic cells and specifically bound to MIF and CD74 in a dot-blot setting. Murine bone-marrow dendritic cells preincubated with Rb9 for 6 h were treated with MIF for short time periods. The modulated responses showed stimulation of CD74 and inhibition of pPI3K, pERK, and pNF-kappa B as compared to MIF alone. Rb9 in a melanoma-conditioned medium, stimulated the M1 type conversion in bone marrow-macrophages. Functional aspects of Rb9 in vivo were studied in therapeutic and prophylactic protocols using a melanoma metastatic model. In both protocols Rb9 exhibited a marked anti-melanoma protection. Human dendritic cells were also investigated showing increased expression of surface markers in response to Rb9 incubation. Rb9 either stimulated or slightly inhibited moDCs submitted to inhibitory (TGF-beta and IL-10) or activating (LPS) conditions, respectively. Lymphocyte proliferation was obtained with moDCs stimulated by Rb9 and tumor cell lysate. In moDCs from cancer patients Rb9 exerted immunomodulatory activities depending on their functional status. The peptide may inhibit over-stimulated cells, stimulate poorly activated and suppressed cells, or cause instead, little phenotypic and functional alterations. Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-gamma, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures

Structural and magnetic properties of core-shell Au/Fe3_3O4_4 nanoparticles

We present a systematic study of core-shell Au/Fe$_3$O$_4$ nanoparticles produced by thermal decomposition under mild conditions. The morphology and crystal structure of the nanoparticles revealed the presence of Au core of $d$ = (6.9 ± 1.0) nm surrounded by Fe$_3$O$_4$ shell with a thickness of ~3.5 nm, epitaxially grown onto the Au core surface. The Au/Fe$_3$O$_4$ core-shell structure was demonstrated by high angle annular dark field scanning transmission electron microscopy analysis. The magnetite shell grown on top of the Au nanoparticle displayed a thermal blocking state at temperatures below $T_\text{B}$ = 59 K and a relaxed state well above $T_\text{B}$. Remarkably, an exchange bias effect was observed when cooling down the samples below room temperature under an external magnetic field. Moreover, the exchange bias field ($H_\text{EX}$) started to appear at $T$~40 K and its value increased by decreasing the temperature. This effect has been assigned to the interaction of spins located in the magnetically disordered regions (in the inner and outer surface of the Fe$_3$O$_4$ shell) and spins located in the ordered region of the Fe$_3$O$_4$ shell.This work was supported by the Brazilian agencies CNPq and CAPES (BEX 6932/15-0) through a financial support in the PhD Student Exchange Program performed in the Institute of Nanoscience of Aragón. The work in Spain was also supported by the Spanish Ministerio de Economia y Competitividad (MINECO) through project MAT2013-42551 and the Aragon Regional Government (DGA, Project No. E26) Technical support from LMAINA and SAI-UZ is acknowledged

Use of functional feeding strategies to protect Atlantic salmon from virally-induced inflammatory diseases- mechanistic insights revealed by transcriptomic analysis

Over the past few years one of the major concerns in the Atlantic salmon (Salmo salar) farming industry has been the increasing incidence and severity of inflammatory viral diseases. Heart and skeletal muscle inflammation (HSMI) and cardiomyopathy syndrome (CMS) are currently two of the most prevalent viral diseases in commercial Atlantic salmon farms in Norway. Mortality levels in both diseases are generally low but morbidity can be very high with the associated chronic inflammatory response lasting for several months. The consequent reduced growth performance is causing considerable financial impact as HSMI has become increasingly widespread in recent years. The impact of CMS is further exacerbated as it generally affects large fish close to harvest. HSMI lesions occur in the atrium and ventricle in the heart including inflammation and necrosis in epi- endo- and myocardium along with myositis of red skeletal muscle. CMS lesions are commonly observed in the spongy myocardium in the atrium and ventricle of the heart with severe mononuclear inflammation and necrosis. Furthermore, circulatory disturbances associated with reduced cardiac function cause multifocal liver steatosis and necrosis in both diseases. Currently there are no vaccines or any other effective treatments for these diseases and so alternative therapies that could potentially modulate the intensity of the inflammatory response could be crucial to improve the clinical manifestation of the diseases. Therefore, the overall aim of the present study was to evaluate the concept of “clinical nutrition” to improve the clinical symptoms of both viral diseases, HSMI and CMS, through the use of functional feeds formulated with reduced lipid content and increased proportions of anti-inflammatory fatty acids to moderate the apparently uncontrolled inflammatory response in the heart tissue associated with both diseases and also alleviate the secondary hepatic lesions. The experimental work consisted of three major dietary trials in Atlantic salmon in seawater. Two large trials investigated the effects of functional feeds in Atlantic salmon challenged with Atlantic salmon piscine reovirus (ASRV) and piscine myocarditis virus (PMCV), the causal agents of HSMI and CMS, respectively. In both trials, heart transcriptome, heart and liver histopathology and tissue lipid and fatty acid compositions and metabolism were determined post-infection in fish fed with the functional feeds in comparison with fish fed with a standard commercial feed formulation considered as a reference diet. All the functional feeds were formulated to have reduced digestible energy through lower dietary lipid and higher protein contents, and increased levels and proportions of anti-inflammatory long-chain polyunsaturated fatty acids (LC-PUFA), particularly eicosapentaenoic acid (EPA) compared with the reference diets. Histopathology, fatty acid composition and gene expression of heart were assessed over a long time-period of 16 weeks and 14 weeks post-challenge with ASRV and PMCV, respectively. Viral load in heart tissue, hepatic histopathology and fatty acid composition of liver and head kidney along with expression of the genes involved in the eicosanoid and LC-PUFA and eicosanoid biosynthesis pathways were also determined in the HSMI trial. The third trial was a nutritional trial evaluating the effects of dietary digestible energy content on lipid and fatty acid metabolism in salmon fed diets containing graded amounts of lipid. Fatty acid composition of liver and heart were assessed over 12 weeks, along with the hepatic expression of genes of lipid and fatty acid metabolism. The results of this research are presented in four chapters (Chapters 2-5) as four paper manuscripts. The manuscripts/Papers are either published (Chapter 2), in review (Chapter 3 and 4) or drafted for submission (Chapter 5) in appropriate peer-reviewed international journals. Chapter 2 and 3 correspond to the HSMI trial, Chapter 4 to the nutritional trial, and Chapter 5 to the CMS trial. Chapter 2 showed that viral load and histopathology scores were lower in fish fed the functional feeds, especially diet FF1, which displayed better performance. Diet strongly influenced the expression of genes related with the immune and inflammatory responses, with delayed expression in fish fed the functional feeds. Up-regulation of pro-inflammatory genes was correlated with the higher viral load observed at early-mid stages of the disease in fish fed the reference diet (ST). Expression of genes related with the immune response at 16-weeks post challenge reflected the differences in immunomodulation between the functional feeds, with fish fed diet FF1 showing lower expression. Therefore, severity of the heart lesions was correlated with the intensity of the immune response and could be associated with tissue anti-inflammatory LC-PUFA levels. Chapter 3 was focused on liver histopathology, fatty acid composition and LC-PUFA biosynthesis, along with phospholipid fatty acid composition and eicosanoid production in head kidney and heart tissue at early and late stages of ASRV infection. Liver was severely affected by the virus at the beginning of the infection in fish fed the reference ST diet, but the level of lesions were similar in all dietary groups at the end of the trial. Hepatic expression of fatty acyl desaturases was significantly depressed in fish fed the ST diet compare with fish fed the functional feeds despite the lower levels of dietary LC-PUFA in that feed. Thus endogenous production and bioavailability of anti-inflammatory LC-PUFA was potentially enhanced in fish fed the functional feeds. Changes in tissue lipid content, mobilization of fatty acids involved in inflammatory responses and changes in expression of transcription factors and genes involved in eicosanoid biosynthesis were more prominent in head kidney, confirming the important role of this organ in dietary immunomodulation after viral infection. To a lesser extent similar changes were observed in heart tissue, suggesting in situ production of eicosanoids could also be important. The unexpected effects of diet on expression of genes of LC-PUFA biosynthesis were specifically investigated in the trial described in Chapter 4. One aim of this study was to clarify whether dietary lipid content or viral infection was the cause of altered expression of desaturase genes between the different diets. Hepatic expression of other genes of lipid and fatty acid metabolism were also determined to evaluate metabolic changes associated with dietary lipid/energy level. In general, reduction of dietary energy and lipid contents while maintaining similar proportions of dietary fatty acids, led to a general up-regulation of genes involved in lipid biosynthetic pathways. Thus salmon fed lower energy diet showed increased liver expression of fatty acyl desaturases in comparison with fish fed higher energy levels. Heart transcriptomic data in Chapter 5 showed a similar delay in the inflammatory response in fish fed the functional feeds after PCMV infection as observed in the HSMI study. Modulation of inflammatory responses, similar to that previously described after ASRV infection, was also observed in fish fed the functional feeds. However, the differences in the expression of immune related genes and the level of heart lesions were not as prominent at mid-late stages of the disease as in fish fed FF1 in the HSMI trial. The present study demonstrated the beneficial effects of a clinical nutrition approach via functional feeds in two viral inflammatory diseases, HSMI and CMS, currently affecting farmed Atlantic salmon. Dietary immunomodulation increased the availability of anti-inflammatory LC-PUFA and significantly influenced the expression of the genes related with the immune/inflammatory response reducing the level and severity of cardiac and liver lesions and therefore improving the performance of fish suffering the diseases

Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1

<p>Abstract</p> <p>Background</p> <p>Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin γ and κ-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against <it>Plasmodium vivax</it>.</p> <p>Methods</p> <p>Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to <it>P. vivax </it>apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses.</p> <p>Results</p> <p>IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (<it>P </it>= 0.004, <it>P </it>= 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype.</p> <p>Conclusions</p> <p>Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to <it>P. vivax </it>malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.</p

Cataloging Coding Sequence Variations in Human Genome Databases

BACKGROUND: With the recent growth of information on sequence variations in the human genome, predictions regarding the functional effects and relevance to disease phenotypes of coding sequence variations are becoming increasingly important. The aims of this study were to catalog protein-coding sequence variations (CVs) occurring in genetic variation databases and to use bioinformatic programs to analyze CVs. In addition, we aim to provide insight into the functionality of the reference databases. METHODOLOGY AND FINDINGS: To catalog CVs on a genome-wide scale with regard to protein function and disease, we investigated three representative databases; the Human Gene Mutation Database (HGMD), the Single Nucleotide Polymorphisms database (dbSNP), and the Haplotype Map (HapMap). Using these three databases, we analyzed CVs at the protein function level with bioinformatic programs. We proposed a combinatorial approach using the Support Vector Machine (SVM) to increase the performance of the prediction programs. By cataloging the coding sequence variations using these databases, we found that 4.36% of CVs from HGMD are concurrently registered in dbSNP (8.11% of CVs from dbSNP are concurrent in HGMD). The pattern of substitutions and functional consequences predicted by three bioinformatic programs was significantly different among concurrent CVs, and CVs occurring solely in HGMD or in dbSNP. The experimental results showed that the proposed SVM combination noticeably outperformed the individual prediction programs. CONCLUSIONS: This is the first study to compare human sequence variations in HGMD, dbSNP and HapMap at the genome-wide level. We found that a significant proportion of CVs in HGMD and dbSNP overlap, and we emphasize the need to use caution when interpreting the phenotypic relevance of these concurrent CVs. Combining bioinformatic programs can be helpful in predicting the functional consequences of CVs because it improved the performance of functional predictions

Genotype-specific responses in Atlantic salmon (Salmo salar) subject to dietary fish oil replacement by vegetable oil: a liver transcriptomic analysis

<p>Abstract</p> <p>Background</p> <p>Expansion of aquaculture is seriously limited by reductions in fish oil (FO) supply for aquafeeds. Terrestrial alternatives such as vegetable oils (VO) have been investigated and recently a strategy combining genetic selection with changes in diet formulations has been proposed to meet growing demands for aquaculture products. This study investigates the influence of genotype on transcriptomic responses to sustainable feeds in Atlantic salmon.</p> <p>Results</p> <p>A microarray analysis was performed to investigate the liver transcriptome of two family groups selected according to their estimated breeding values (EBVs) for flesh lipid content, 'Lean' or 'Fat', fed diets containing either FO or a VO blend. Diet principally affected metabolism genes, mainly of lipid and carbohydrate, followed by immune response genes. Genotype had a much lower impact on metabolism-related genes and affected mostly signalling pathways. Replacement of dietary FO by VO caused an up-regulation of long-chain polyunsaturated fatty acid biosynthesis, but there was a clear genotype effect as fatty acyl elongase (elovl2) was only up-regulated and desaturases (Δ5 fad and Δ6 fad) showed a higher magnitude of response in Lean fish, which was reflected in liver fatty acid composition. Fatty acid synthase (FAS) was also up-regulated by VO and the effect was independent of genotype. Genetic background of the fish clearly affected regulation of lipid metabolism, as PPARα and PPARβ were down-regulated by the VO diet only in Lean fish, while in Fat salmon SREBP-1 expression was up-regulated by VO. In addition, all three genes had a lower expression in the Lean family group than in the Fat, when fed VO. Differences in muscle adiposity between family groups may have been caused by higher levels of hepatic fatty acid and glycerophospholipid synthesis in the Fat fish, as indicated by the expression of FAS, 1-acyl-sn-glycerol-3-phosphate acyltransferase and lipid phosphate phosphohydrolase 2.</p> <p>Conclusions</p> <p>This study has identified metabolic pathways and key regulators that may respond differently to alternative plant-based feeds depending on genotype. Further studies are required but data suggest that it will be possible to identify families better adapted to alternative diet formulations that might be appropriate for future genetic selection programmes.</p