For Asia, rates for typhoid fever and shigellosis declined, where

For Asia, rates for typhoid fever and shigellosis declined, whereas rates for hepatitis A remained stable. This finding may reflect the disproportionate impact of the Indian subcontinent, with stable trends, on trends for Asia overall: 75% of all Asian hepatitis A cases were contracted in the Indian subcontinent, compared to <60% for shigellosis and typhoid fever (data not shown). The trends in attack rates we found

for hepatitis A and typhoid fever correlate with findings in other studies.5–7 One study on travel-related shigellosis discusses only absolute attack rates; these correlate with the median rates we calculated.17 The Dutch policy not to recommend typhoid fever vaccination for Ivacaftor short-term travelers to Latin America, Eastern/Southern Sub-Saharan Africa, Turkey, and Thailand/Malaysia appears to be justified, because

median attack rates for these destinations were less than 0.2 per 100,000 travelers (Table 2), and vaccine-failure occurred in at least 21% of cases (Table 1). This study has some possible limitations. Although the three infections are comparable in their mode of transmission, they differ in ways that influence reporting. For example, the short incubation period for shigellosis (1–7 d) as opposed to hepatitis A (2–7 wk) increases its chance Y-27632 chemical structure of occurring abroad, decreasing its chance of being reported in the Netherlands. Also, the three diseases differ in degree of asymptomatic infection, patients’ medical attention-seeking behavior, and doctors’ tendency to request laboratory confirmation. Hepatitis A virus infection in childhood is often asymptomatic, but occurs with varying severity of illness in adults. In typical shigellosis, stools contain blood and mucus, but may also present as watery diarrhea or asymptomatic infection. Typhoid fever symptoms can likewise range from asymptomatic to severe. Susceptibility for the latter two increases in a setting of gastric achlorhydria or immunosuppression. These variations in disease severity undoubtedly influence the chance of being diagnosed,

and thus the chance of being reported. However, there are no reasons to believe that the impact of these factors changed during the study period. Thus, they have led only to an underestimation of the annual Fluorouracil attack rates, without affecting trends in attack rates. Serology is not an accurate method for the diagnosis of typhoid fever, because of cross-reactivity. However, the proportion of serological confirmed cases was low (6.4%), and it did not change during the study period. Thus, trends in attack rates were not affected. In our study, the number of annually reported cases was put into perspective by using numbers of travelers as denominators. The latter are crude estimates. Country-specific data were used after classification into regions to render findings more robust.

For Asia, rates for typhoid fever and shigellosis declined, where

For Asia, rates for typhoid fever and shigellosis declined, whereas rates for hepatitis A remained stable. This finding may reflect the disproportionate impact of the Indian subcontinent, with stable trends, on trends for Asia overall: 75% of all Asian hepatitis A cases were contracted in the Indian subcontinent, compared to <60% for shigellosis and typhoid fever (data not shown). The trends in attack rates we found

for hepatitis A and typhoid fever correlate with findings in other studies.5–7 One study on travel-related shigellosis discusses only absolute attack rates; these correlate with the median rates we calculated.17 The Dutch policy not to recommend typhoid fever vaccination for www.selleckchem.com/products/i-bet-762.html short-term travelers to Latin America, Eastern/Southern Sub-Saharan Africa, Turkey, and Thailand/Malaysia appears to be justified, because

median attack rates for these destinations were less than 0.2 per 100,000 travelers (Table 2), and vaccine-failure occurred in at least 21% of cases (Table 1). This study has some possible limitations. Although the three infections are comparable in their mode of transmission, they differ in ways that influence reporting. For example, the short incubation period for shigellosis (1–7 d) as opposed to hepatitis A (2–7 wk) increases its chance GSK2118436 concentration of occurring abroad, decreasing its chance of being reported in the Netherlands. Also, the three diseases differ in degree of asymptomatic infection, patients’ medical attention-seeking behavior, and doctors’ tendency to request laboratory confirmation. Hepatitis A virus infection in childhood is often asymptomatic, but occurs with varying severity of illness in adults. In typical shigellosis, stools contain blood and mucus, but may also present as watery diarrhea or asymptomatic infection. Typhoid fever symptoms can likewise range from asymptomatic to severe. Susceptibility for the latter two increases in a setting of gastric achlorhydria or immunosuppression. These variations in disease severity undoubtedly influence the chance of being diagnosed,

and thus the chance of being reported. However, there are no reasons to believe that the impact of these factors changed during the study period. Thus, they have led only to an underestimation of the annual Selleck RG7420 attack rates, without affecting trends in attack rates. Serology is not an accurate method for the diagnosis of typhoid fever, because of cross-reactivity. However, the proportion of serological confirmed cases was low (6.4%), and it did not change during the study period. Thus, trends in attack rates were not affected. In our study, the number of annually reported cases was put into perspective by using numbers of travelers as denominators. The latter are crude estimates. Country-specific data were used after classification into regions to render findings more robust.

In addition, the intromission of ‘alien’ microorganisms and globa

In addition, the intromission of ‘alien’ microorganisms and global warming are strongly affecting microbial Antarctic populations, giving us an insight into new genetic evolutionary forces. This changing environment, rich in cold-adapted bacteria, is a genomic source for the identification of novel molecules and provides DNA elements suitable selleck for the design of new recombinant technologies. Extensive research has shown the potential of the Antarctic bacterial

DNA in the development of genetic engineering vectors to produce heterologous proteins at low temperature. The isolation by either culture-dependent or culture-independent approaches of genes responsible for producing cold-active enzymes with many potential biotechnological applications had also been

successful. Antarctic bacterial DNA is a valuable resource that is a substantial biotechnological resource that must be preserved. Authors thank Programa De Desarrollo de las Ciencias Básicas (PEDECIBA), Uruguay, and Instituto Antártico Uruguayo (IAU). C.M.-R. was supported by Agencia Nacional de Investigación e Innovación (ANII). C.M.-R. and N.F. contributed equally to this work. “
“Dona Paula, Goa, India Studies on the molecular diversity of the micro-eukaryotic community have shown that fungi occupy a central position in a large number of marine habitats. Environmental surveys using molecular tools have shown the presence of fungi from a large number of marine BAY 80-6946 chemical structure habitats such as deep-sea habitats, pelagic waters, coastal regions, hydrothermal vent ecosystem, anoxic habitats, and ice-cold regions. This is of Pyruvate dehydrogenase lipoamide kinase isozyme 1 interest to a variety of research disciplines like ecology,

evolution, biogeochemistry, and biotechnology. In this review, we have summarized how molecular tools have helped to broaden our understanding of the fungal diversity in various marine habitats. Majority of the environmental phylotypes could be grouped as novel clades within Ascomycota, Basidiomycota, and Chytridiomycota or as basal fungal lineages. Deep-branching novel environmental clusters could be grouped within Ascomycota as the Pezizomycotina clone group, deep-sea fungal group-I, and soil clone group-I, within Basidiomycota as the hydrothermal and/or anaerobic fungal group, and within Chytridiomycota as Cryptomycota or the Rozella clade. However, a basal true marine environmental cluster is still to be identified as most of the clusters include representatives from terrestrial regions. The challenge for future research is to explore the true marine fungi using molecular techniques. “
“Large plasmids (‘megaplasmids’) are commonly found in members of the Alphaproteobacterial family Sphingomonadaceae (‘sphingomonads’). These plasmids contribute to the extraordinary catabolic flexibility of this group of organisms, which degrade a broad range of recalcitrant xenobiotic compounds. The genomes of several sphingomonads have been sequenced during the last years.

Maraviroc and raltegravir were not included in this study as FDA

Maraviroc and raltegravir were not included in this study as FDA approval for these agents occurred near the end of our evaluation period. For persons starting more than one of the target medications over the study period, the first VHA out-patient prescription

for each target medication was counted. To reduce the number of prescriptions for patients whose care was transferred to the VHA and who were already on a medication of interest, only veterans with out-patient prescription records for at least 1 quarter (90 days) prior to their first prescription for a target medication were included. For each quarter post-approval, we measured the uptake of each medication, defined as the number of new patients with prescriptions for the medication. The start dates for the first quarter for each agent were: atazanavir, selleck June 2003; darunavir, June 2006; tipranavir, June 2005; and lopinavir/ritonavir, September 2000. For each quarter, we determined the number of providers who first wrote a new prescription for one of the four medications and the HM781-36B purchase number of providers who prescribed any antiretroviral. Based on provider type, providers were categorized as physician, physician trainee (student/resident/fellow) or physician extender (nurse/physician assistant/clinical pharmacist).

Clinics where prescriptions were initiated were categorized as infectious disease (ID), primary care or other. VAV2 For each quarter we determined

the cumulative number of facilities that had prescribed each of the target medications. Based on the facility location of the qualifying new out-patient prescription, the prescription was assigned to a Centers for Disease Control and Prevention (CDC) geographical region: Northcentral, Northeast, South or West. To provide a benchmark for the regional uptake of new antiretrovirals, we determined the total number of antiretroviral prescription fills during the period from March 2003 (3 months prior to the earliest approval date for a target medication) to December 2007. For comparison, if the uptake of a new medication matched the prescribing of other antiretrovirals, the percentage of the new prescriptions occurring in a specific region should match the percentage of all antiretroviral fills for that region. For example, if 20% of all antiretroviral fills occurred in the West then one would expect the West to account for 20% of the new prescriptions for a target medication; if the West accounted for >20% of the new prescriptions for a medication, that would indicate that the West had greater uptake of the medication than expected. Medication uptake by region was determined for three time periods: quarters 1 and 2 post FDA approval (period 1), quarters 3–6 post-approval (period 2), and quarters 7+ post-approval until 31 December 2007 (period 3).

Furthermore, scl-L4, which encodes serine hydroxymethyltransferas

Furthermore, scl-L4, which encodes serine hydroxymethyltransferase (SHMT), has been identified using both SCOTS and STM (Harper et al., 2003). The glyA gene, encoding SHMT, was shown to be essential in E. coli (Yan et al., 2002). It belongs to the pur regulon, which is required for purine synthesis in E. coli (Steiert et al., 1990). The AL393 mutant of P. multocida, which has a probable effect on glyA function, was attenuated only in chickens in STM (Harper et al., SCH772984 chemical structure 2003). Clone scs-L15 corresponds to the gene encoding a polynucleotide phosphorylase (Pnp) that

is involved in the degradation of mRNA. In a previous study using STM, a pnp mutant of P. multocida was identified and found to be attenuated in mice (Fuller et al., 2000). Meanwhile, pnp was found to be required for the expression of plasmid-borne virulence genes in Shigella flexneri, using STM (Tobe et al., 1992). The clone scs-L13, homologous to the fhaB1/fhaB2

gene that encodes filamentous hemagglutinin, harbors a potential virulence factor. Using STM in a model of septicemia in the mouse, the fhaB1 and fhaB2 genes from a case of bovine pneumonia were identified, and an fhaB2 knockout mutant was engineered using a temperature-sensitive plasmid in a well-known virulent strain of P. multocida A: 3 (P-1059) (Fuller et al., 2000). The virulence of the ΔfhaB2 mutant was attenuated in Beltsville white turkeys following intranasal administration, and fhaB2 peptides were evaluated in the

natural host (Tatum et al., 2005). The fhaB1 gene was inserted using see more a kanamicin-resistant gene, and the ΔfhaB1 mutant of P. multocida strain C48-102 was attenuated when administered via intranasal injection (our data). In contrast, some scs-L clones showed homology to the upregulated genes found in other pathogenic bacteria, including those expressed during natural and/or experimental infection or under in vitro growth conditions that mimicked an in vivo environment. Clones scs-L18, scs-L22, and scs-L24 encode cell division protein FtsQ, translation elongation factor EF-Tu (TufA), and ATP-stimulated mitochondrial matrix protein Chlormezanone (Lon protease), respectively. Fittipaldi and colleagues, using SCOTS, identified the ftsQ/divIB gene that is expressed preferentially by S. suis upon interaction with porcine brain microvascular endothelial cells (Fittipaldi et al., 2007). However, FtsQ was downregulated when recovered from the blood of chickens infected with P. multocida (Boyce et al., 2002). FtsQ/divIB is a highly conserved component of the divisome that plays a central role in the assembly of the early and late cell division proteins FtsL and FtsB/DivIC (Robson & King, 2006; Gonzalez et al., 2010). The ftsQ and divIB genes are homologous; ftsQ was essential in E.

, 1998; Aoki et al, 2000) However, in the current study, false-

, 1998; Aoki et al., 2000). However, in the current study, false-positive amplifications with the primer sets SA1B10-1-F and SA1B10-1-R3, LG-1 and pLG-2, and cG-F and Lc-R5 were observed for genomic DNA of L. lactis subsp. lactis, Enterococcus casseliflavus, Enterococcus solitarius, Streptococcus pyogenes, and Streptococcus anginosus. Therefore, the new DNA signatures CAUF58 and CAUF64 show higher specificity for PCR-based detection

of L. garvieae compared with those of the current primers. Lactococcus garvieae, the leading agent of lactococcosis, affects many fish species worldwide. In addition, this bacterium is considered a potential zoonotic microorganism because it is known to cause human infections, and L. garvieae outbreaks in humans have recently been reported in Italy (Reimundo et al., 2011). Our data indicate that SSH can be exploited for the development of more stable and robust chromosome-specific selleck chemical DNA signatures that will supplement the previously reported diagnostic markers including 16S rRNA for accurate identification of L. garvieae. This paper was sponsored by Wonkwang University in 2010. W.K. and H.K.P. contributed equally to this work. “
“A lipopolysaccharide mutant of Leptospira interrogans (LaiMut) was obtained by growth in the presence of an agglutinating monoclonal

antibody (mAb) against lipopolysaccharide. ABT-263 molecular weight Agglutination reactions with anti-lipopolysaccharide mAbs and polyclonal antibodies showed that LaiMut had lost some serogroup Icterohaemorrhagiae agglutinating epitopes. However, LaiMut displayed an increased reactivity to antisera against related serogroups,

suggesting that the disruption Idelalisib mw of some lipopolysaccharide epitopes resulted in greater exposure to cross-reactive epitopes, not accessible to antibodies in the wild type (LaiWT). Comparison of the nucleotide sequences of the lipopolysaccharide loci of LaiMut and Lai wild type (LaiWT) strains showed an inframe stop mutation in the gene encoding undecaprenyl-galactosyltransferase, a protein that provides a fundamental and nonredundant function essential for lipopolysaccharide biosynthesis. Despite this, the biosynthesis of lipopolysaccharide agglutinating antigens was not abolished by the mutation. Based on the phenotype of LaiMut and analysis of the domain structure of the undecaprenyl-galactosyltransferase in relation to the mutation, we propose that the mutation results in the expression of two functional proteins in place of the undecaprenyl-galactosyltransferase. We hypothesize that the loss of coordination of the coupled function afforded by the intact dual function protein present in the parent strain results in an inefficient production of lipopolysaccharide in LaiMut. The genus Leptospira is classified genetically into more than 17 species, which can be more generally classified into three groups based on the genetic relationships between the species; these groups comprise the pathogenic, saprophytic, and intermediate species (Morey et al., 2006).

Twenty-five patients who met the American College of Rheumatology

Twenty-five patients who met the American College of Rheumatology 1987 revised diagnostic criteria for RA were randomly selected for this study. The percentage of brachial flow-mediated dilation buy Paclitaxel (%FMD) and maximum carotid intima-media thickness were examined by ultrasonography. The %FMD in the group treated with anti-TNF therapy was significantly higher than that in the group treated with DMARDs (P < 0.001). The %FMD was significantly correlated with anti-TNF therapy (r = 0.684, P < 0.001) and Disease Activity Score C-reactive protein (r = –0.404, P < 0.05).

Multiple regression analysis revealed that anti-TNF therapy was significantly associated with %FMD (β = 0.684, P < 0.001). Anti-TNF therapy may influence endothelial function more than conventional DMARD therapy. Prospective longitudinal studies examining whether anti-TNF therapy was able to improve endothelial function are required. Rheumatoid arthritis RNA Synthesis inhibitor (RA) is a disease associated with increased cardiovascular mortality, resulting from accelerated atherosclerosis.[1, 2] Endothelial dysfunction is an early step in atherogenesis,[3] which may be determined by non-invasive techniques such as brachial ultrasonography (US) which measures flow-mediated endothelium-dependent

vasodilation.[4, 5] Endothelial dysfunction determined by flow-mediated endothelium-dependent vasodilation (FMD) has been observed in both patients with recent onset and low disease activity as well as long-standing RA patients.[6, 7] Hannawi[8] recently reported that carotid

intima-media thickness (IMT) is greater in RA patients with recent disease onset than Farnesyltransferase in age- and sex-matched control individuals. IMT is a useful noninvasive surrogate marker of macrovascular atherosclerosis disease. Gonzalez-Juanatey et al. report the presence of increased IMT in RA patients and a strong correlation between C-reactive protein (CRP) levels and the presence of subclinical atherosclerosis in these patients.[9] Recently, several authors investigated the effects of atherosclerosis on endothelial function or IMT during biologics treatment in patients with RA.[10-14] Patients with RA refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs) exhibited short-term improvement in endothelial dysfunction following anti-tumor necrosis factor (TNF)-alpha therapy.[10, 12] However, the effects of some anti-TNF drugs seem to be transient.[11] Consistent with these findings, other biological therapies such as rituximab have also been reported to improve endothelial dysfunction in patients with RA refractory to anti-TNF drugs.[13, 15] On the basis of these findings, we aimed to clarify whether different TNF drugs can improve endothelial function better than conventional DMARDs in a series of Japanese patients with RA.

Several phylotypes were affiliated with unclassified environmenta

Several phylotypes were affiliated with unclassified environmental clone groups, UBSedI to VI and UBMnI and II, as defined in the present study (Fig. S2e). Phylotypes in the Gammaproteobacteria were abundant in the clone libraries from the Mn crust and sediment samples (24.0% and 23.5% of the total

clone numbers, respectively; Fig. 3). These phylotypes were related to not yet cultivated environmental clones recovered from seafloor basaltic rocks (Lysnes et al., 2004; Mason et al., PLX-4720 mouse 2007, 2008; Santelli et al., 2008) rather than cultured species (<95% similarity) (Fig. S2b). In contrast, phylotypes in the Alphaproteobacteria were abundant in the clone libraries from the seawater sample (44.3% of the total clone number). In particular, most of them were related to Candidatus Pelagibacter (SAR11 cluster, Rappéet al., 2002) and Sphingomonadales (Fig. S2c), groups from which members have often been recovered from deep-sea water of >1000 m water depth (García-Martínez & Rodríguez-Valera, 2000; Delong et al., 2006; Kato et al., 2009a, c). Comparative analysis showed that the microbial community composition of the Mn crust was different from those of the sediment and overlying seawater. The differences

among the three communities were supported by the UniFrac significance and P values (<0.01). To compare the microbial community composition, the shared phylotype numbers among the libraries from the crust, sediment FAD and seawater

samples were estimated selleck chemicals llc using sons. The Mn crust and sediment communities shared few or no phylotypes with the seawater community (Fig. 4). The Mn crust community contained a fraction of phylotypes recovered from the sediment sample (20% of the total phylotype richness estimates of the Mn crust; Fig. 4). Thus, 80% of the total phylotypes richness estimates of the Mn crust community were unique compared with the sediment communities. In fact, unique phylotypes of the Mn crust were observed in the phylogenetic trees (Fig. S2). Several phylotypes in MGI were shared between the Mn crust and sediment, but not between the Mn crust and seawater (Fig. S2a) as described above. Phylotypes related to the genus Nitrosospira in the Betaproteobacteria were unique in the Mn crust (Fig. S2b). Representative clone 953Mn48u has 97% similarity to the ammonia-oxidizing chemolithoautotrophic bacterium Nitrosospira multiformis (Watson et al., 1971). Phylotypes related to the family Ectothiorhodospiraceae in the Gammaproteobacteria were also unique in the library of the Mn crust (Fig. S2b). Representative clone 953Mn100u has 94% similarity to the arsenite-oxidizing chemolithoautotroph Alkalilimnicola ehrlichii (Hoeft et al.

However, the increasing use of insulin analogues poses a challeng

However, the increasing use of insulin analogues poses a challenge because commercially available insulin assays detect these with varying accuracy and precision. Insulin analogues are increasingly used in diabetes management and the case outlined here highlights the variations in assay. Initially, the local assay (ELISA kit – Dako, Copenhagen) failed to detect a significant concentration of insulin (<6pmol/L; range 9.6–65.4pmol/L) which an external reference laboratory CDK inhibitor subsequently detected using the Mercodia Iso-insulin two-site

immunoassay (Uppsala, Sweden). The key analytical point is the recognition that different immunoassays detect insulin analogues to varying degrees. Clinical teams need to consider this if such cases are to be recognised. Following recent media reports where surreptitious insulin administration may be implicated in inpatient mortality, this knowledge is crucial to empower us to STA-9090 molecular weight accurately diagnose all cases of unexplained hypoglycaemia. Copyright © 2013 John Wiley & Sons. Practical Diabetes 2013; 30(3): 118–120 “
“The evolution of diabetes centres in the UK, with co-location of clinical

teams, has resulted in examples of success in improving clinical efficiency, communication and patient-centred care. “
“Erectile dysfunction (ED) is expected to affect 322 million men by 2025. A number of lifestyle factors such as smoking, obesity, alcohol consumption and lack of physical activity are linked with erectile dysfunction. We reviewed the evidence in

recent studies examining the impact of weight loss upon erectile function in obese men with and without diabetes. Esposito et al. showed that weight loss through diet and increased physical activity can improve sexual function in about one-third of obese non-diabetic men with ED. Subsequently, Dallal et al. reported that the amount of surgical weight loss after gastric bypass predicted the degree of improvement in sexual function independent of improvement in glycaemic control. Wing et al. reported Cepharanthine that weight loss in older obese diabetic subjects in the Look AHEAD trial may help in preventing the worsening of ED over time. Most recently in 2011, Khoo et al. have shown that rapid diet-induced weight loss improves sexual and endothelial function and systemic inflammation in obese diabetic men. In conclusion, the majority of recent studies show that weight loss can improve erectile function in obese men, though the beneficial effect is less profound in diabetic men. Copyright © 2012 John Wiley & Sons. “
“It is a myth that screening of type 2 diabetes is ‘a given’, that we provide adequate education for patients and that increasing physical activity by simply referring patients to a health trainer can prevent type 2 diabetes. Research in this area is often seen as an easy or soft option.

, 2008) Because expression of the sdrP gene was also enhanced by

, 2008). Because expression of the sdrP gene was also enhanced by other stresses, cross-protection may occur via SdrP in T. thermophilus HB8. We wish to thank Keiko Sakamoto for the RT-PCR analysis. We also thank Noriko Nakagawa, Aiko Kashihara, Emi Ishido-Nakai, Miwa Ohmori, Kenji Fukui,

Takushi Ooga, Toshiko Miyazaki, and Keiko Sakamoto for their excellent support in the GeneChip analysis, and Kazuko Agari for the excellent support with preparation of the templates for the in vitro transcription assays. Fig. S1. Expression pattern analysis using DNA microarray data. Fig. S2. Identification of the transcriptional start site. Table S1. GEO accession numbers and experimental conditions for the DNA microarray dataset. Table S2. Oligonucleotides used in MK-1775 this study. Table S3. Number of genes correlated with sdrP

gene in each COGs category. Table S4. Genes exhibiting Spearman’s correlation coefficients, as to the sdrP gene, of ≥0.50. Table S5. Genes exhibiting Spearman’s correlation coefficients as to the sdrP gene, of ≤-0.50. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Four bacterial strains capable of growing in the presence of tannic acid as sole carbon and energy source were isolated from olive mill waste mixtures. 16S rRNA gene AZD1208 sequencing assigned them to the genus Klebsiella. The most efficient strain, Klebsiella sp. strain C2A, was able to degrade 3.5 g L−1 tannic acid within 35 h with synthesizing gallic acid as main product. The capability of Klebsiella sp. strain C2A to produce tannase was evidenced at high concentrations of tannic acid up to 50 g L−1. The bacteria adapted to the toxicity of tannic acids by an increase in the membrane lipid fatty acids degree of saturation, especially in the presence of concentrations higher than 20 g L−1. The highly tolerant and adaptable bacterial strain characterized in this study Tobramycin could be used in bioremediation processes of

wastes rich in polyphenols such as those derived from olive mills, winery or tanneries. “
“The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseriTMC0356 (TMC0356) for 4 and 8 weeks at dosages of 10 mg day−1 after a 16-week period of prefeeding with a standard diet. After 4 and 8 weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8 weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P < 0.05).