Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.

BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.

Anaphylaxis to galacto-oligosaccharides--an evaluation in an atopic population in Singapore.

Anaphylaxis to galacto-oligosaccharides (GOS), a prebiotic, has been described in atopic patients following its supplementation in commercial milk formula in South-East Asia. The epidemiology of this usual allergy to a carbohydrate is unknown. This study evaluated the prevalence of allergy to two formulations of commercial GOS, Vivinal™ GOS (vGOS) and Oligomate™ , in an atopic cohort. Atopic subjects (n = 487) from two specialist allergy clinics were surveyed via structured questionnaire and underwent skin prick tests to GOS. Subjects with positive skin prick tests to GOS (n = 30, 6.2%) underwent basophil activation tests, and a subset (n = 13) underwent oral challenge tests to both formulations of GOS. Six subjects had positive challenges to vGOS; and none to Oligomate. By extrapolating the BAT and oral challenge results, the prevalence of allergy to vGOS is estimated at up to 3.5% (95% CI 2.2-5.5%) of our atopic population. Our findings show that GOS allergy may be common amongst atopics in Singapore.

Trophic size-structure of sailfish Istiophorus platypterus in eastern Taiwan estimated by stable isotope analysis.

To examine trophic dynamics over different size classes, an isotopic study of sailfish Istiophorus platypterus life-history stages was carried out. Samples were collected from eastern Taiwan and the South China Sea during April 2009 and February 2012. A total of 263 samples (111-245 cm, lower jaw fork length, LLJFL ) were examined for changes in trophic structure in relation to LLJFL by using stable isotope analysis of carbon (δ(13) C) and nitrogen (δ(15) N). The δ(15) N values for I. platypterus ranged from 7·51 to 14·19‰ (mean ± s.d. = 12·06 ± 1·16‰) and the δ(13) C values ranged from -22·04 to -15·48‰ (mean ± s.d. = -17·62 ± 1·10‰). The δ(15) N values were positively dependent on LLJFL (r(2) = 0·377), whereas δ(13) C were negatively dependent on LLJFL (r(2) = 0·063). There were significantly different seasonal changes in nitrogen and carbon isotopic concentration, but no significant differences in concentrations between eastern Taiwan and the South China Sea were reported. The trophic level (TL ) of each LLJFL class was correlated, starting from 2·84 TL for size class I (LLJFL < 140 cm) and reaching 5·03 TL for size class VI (LLJFL > 221 cm). The mean ± s.d. TL was 4·43 ± 0·19 for all samples. The results reveal that I. platypterus occupies a wide range of trophic levels and different size classes occupy different trophic positions in the pelagic ecosystem.

Low-temperature water dynamics in an aqueous methanol solution.

An aqueous methanol solution (x(MeOH) = 0.30) has been studied by quasielastic neutron scattering. The single-particle water dynamics were effectively isolated by employing deuterated methanol. A smooth dynamic transition to a sub-Arrhenius temperature dependence has been observed in the relaxation times. We associate this behavior with the formation of small crystallites in the system. These findings are compared with molecular dynamics simulations and previous nuclear magnetic resonance measurements. We discuss possible dynamic signatures of structuring in the mixture.

miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma.

BACKGROUND: MicroRNAs play important roles in carcinogenesis. A preliminary screening study suggested that down-regulation of miR-370 occurs in oral squamous cell carcinoma (OSCC) tissue. Insulin receptor substratre-1 (IRS-1) is the substrate of insulin-like growth factor receptor (IGFR), which modulates AKT/mTOR activation in malignancies. The relationship between miR-370 and IRS-1, and their functional roles in OSCC pathogenesis are unclear. MATERIALS AND METHODS: Primary OSCC specimens were examined for miR-370 expression. Exogenous expression of miR-370 was established using both stable subclones and transient expression, and these were used to gain insights into miR-370's functions in OSCC cells. Knockdown of miR-370 and IRS-1 was also carried out in OSCC cells using a small interference oligonucleotide approach. RESULTS: Squamous cell carcinoma tissues with perineural invasion had lowered miR-370 expression compared with contrasting OSCC. OSCC cells also exhibited lower miR-370 expression than normal oral keratinocytes, and this can be reversed by treatment with 5-aza-2'-deoxycytidine. Exogenous miR-370 expression decreases the migration and anchorage-independent growth of OSCC cells, which implies a suppressor role for miR-370. The enhancement of anchorage-independent growth of OSCC cells through miR-370 inhibiting can be reduced by knockdown of IRS-1 expression. CONCLUSION: This study concludes that miR-370 is able to target IRS-1 for oral tumorigenesis.

Predicting methicillin resistance among community-onset Staphylococcus aureus bacteremia patients with prior healthcare-associated exposure.

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %, comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection.

Simulation and experimental study of a K-band extended interaction oscillator for microwave processing systems.

High-power microwave sources have been widely applied for material processing in scientific research and manufacturing. The development of stable, high-frequency, high-power microwave sources is essential for achieving efficient microwave processing. This study proposes using a square doubly reentrant coupled-cavity as the slow-wave resonant structure in a K-band extended interaction oscillator (EIO). This design allows for ease of fabrication and high-power capability. The EIO is designed to operate in single 0-mode. The simulation results show that the competing π/5-mode can be effectively suppressed by properly choosing the width and location of the output coupler. The simulation and experiments successfully demonstrate stable, single-mode, tunable, high-performance operation of the EIO. The experimental measurements show a maximum output power of 1.776 kW (18.56% electronic efficiency), and a wave frequency of 24.324 GHz at a beam voltage of 17.4 kV and beam current of 550 mA. The EIO microwave source is suitable for interdisciplinary applications that require higher heating rates and greater uniformity.

Isoptericola chiayiensis sp. nov., isolated from mangrove soil.

A novel actinomycete, designated strain 06182M-1(T), was isolated from a mangrove soil sample collected from Chiayi County in Taiwan. Phylogenetic analysis based on 16S rRNA gene sequences revealed levels of similarity of 97.0-98.8 % to the type strains of recognized species of the genus Isoptericola. Chemotaxonomic data also supported the placement of strain 06182M-1(T) within the genus Isoptericola. However, the low levels of DNA-DNA relatedness between the novel strain and the type strains of recognized species of the genus Isoptericola, in combination with differential phenotypic data, demonstrate that strain 06182M-1(T) represents a novel species of the genus Isoptericola, for which the name Isoptericola chiayiensis sp. nov. is proposed. The type strain is 06182M-1(T) ( = BCRC 16888(T)  = KCTC 19740(T)).

Increase of ZASC1 gene copy number in recurrent oral carcinoma.

BACKGROUNDS: The chromosome 3q26 locus is a hotspot region carrying oncogenes that frequently altered in neoplasms. ZASC1 is a zinc finger protein transcription factor localized on 3q26. Our previous study showed the frequent amplification of 3q26, including the ZASC1 gene, in oral squamous cell carcinoma (OSCC). This study investigated the copy number changes of ZASC1 gene from primary to recurrent OSCC and the functions of ZASC1 in OSCC cells. MATERIALS AND METHODS: A total of 27 OSCC patients with primary and recurrent tumors were examined for ZASC1 and TERC copy number changes using Quantitative PCR analysis. Exogenous expression and knockdown of ZASC1 were carried out to specify the oncogenic potential of ZASC1 in OSCC cells. RESULTS: A ZASC1 copy number that has increased from primary to recurrent tumor counterparts in tissue pairs suggested the importance of ZASC1 in tumor progression. The increase of ZASC1 gene copy number in recurrent tumors was associated with the consumption of betel quid in patients. OSCC cells expressing ZASC1-FLAG fusion protein showed increased proliferation. After the knockdown of endogenous ZASC1 expression using small interference RNA, the growth and colony formation of SAS OSCC cells decreased. CONCLUSIONS: The findings support the hypothesis that ZASC1 localized on 3q26 contributes to the recurrence of OSCC.

Characterization of a 6K oligonucleotide turkey skeletal muscle microarray.

Consumer demand for lean, inexpensive meat products has driven the domestic turkey (Meleagris gallopavo) industry to unprecedented production; however, this has coincided with an increase in growth-induced myopathies and meat quality defects. With the aim of developing a new tool for the study of turkey growth and development at the muscle transcriptome level, a 6K oligonucleotide microarray was constructed, the Turkey Skeletal Muscle Long Oligo (TSKMLO) microarray. Skeletal muscle samples were collected at three critical stages in muscle development: 18-day embryo (hyperplasia), 1-day post-hatch (hypertrophy), and 16-week (market age) from two genetic lines of turkeys: RBC2, a line maintained without selection pressure, and F, a line selected from the RBC2 line for increased 16-week body weight. Oligonucleotides were designed from sequences obtained from skeletal muscle cDNA libraries from the three developmental stages. Several unique controls, including mismatch and distance controls and scrambled sequences, were designed for 30 genes. Quality control hybridizations were completed, confirming the validity and repeatability of the array. Control features were evaluated across two larger experiments comparing developmental stage within genetic line or genetic line within each developmental stage, totaling 70 arrays. Mismatch and scrambled sequences appeared to be useful controls of specific hybridization for most genes. In addition, quantitative real-time RT-PCR confirmed microarray results. This creation and assessment of the TSKMLO array provides a valuable community resource for the study of gene expression changes related to turkey muscle growth and development.

Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes.

Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.

Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure.

This observational study enrolled adult patients with bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) who were treated at the emergency department of a teaching hospital from 2001 to 2007. MRSA isolates with type IV and type V staphylococcal cassette chromosome mec (SCCmec) genes (SCC IV/V-MRSA) were included in the final analysis. Healthcare-associated SCC IV/V-MRSA (HA-SCC IV/V-MRSA) and community-acquired SCC IV/V-MRSA (CA-SCC IV/V-MRSA) were defined as the identification of an SCC IV/V-MRSA isolate from a patient with and without healthcare-associated risk factors, respectively. Thirty-four cases of CA-SCC IV/V-MRSA (20 SCCmec type IV, 14 SCCmec type V) and 81 cases of HA-SCC IV/V-MRSA (59 SCCmec type IV, 22 SCCmec type V) bacteremia were identified. Vascular device-associated infections were a significant infection source in HA-SCC IV/V-MRSA bacteremia cases. SCCmec type IV HA-SCC IV/V-MRSA isolates (3.4%) were significantly less likely to carry the Panton-Valentine leukocidin (PVL) gene than SCCmec type IV CA-SCC IV/V-MRSA isolates (35.0%, p = 0.001). The 90-day cumulative probability of survival was 76% for patients with CA-SCC IV/V-MRSA bacteremia and 66% for patients with HA-SCC IV/V-MRSA bacteremia (p = 0.247, by the Wilcoxon rank-sum test). Significant differences in antimicrobial susceptibility were observed between bacterial isolates from patients with CA-SCC IV/V-MRSA bacteremia and HA-SCC IV/V-MRSA bacteremia.

Pale, soft, exudative turkey--The role of ryanodine receptor variation in meat quality.

The poultry industry has made significant advances in growth rate, feed efficiency, and breast muscle yield through intensive breeding of turkeys. However, a meat quality problem known as pale, soft, exudative (PSE) meat presents the industry with a major challenge during periods of stress, such as the onset of a prolonged heat wave. The biochemical characteristics of PSE turkey are strikingly similar to those of PSE pork. Abnormally rapid postmortem metabolism, stimulated in part by high concentrations of calcium ions, may be one of the underlying factors associated with the incidence of PSE turkey. This presentation summarizes our studies on the avian ryanodine receptors and suggests that heat stress may alter the expression pattern of splice variants of ryanodine receptors, which, in turn, could affect postmortem calcium homeostasis.

High performance and high power circularly polarized horn antenna for K-band microwave processing systems.

A single-ridged K-band circularly polarized horn antenna offering excellent performance has been developed by improving the polarization conversion and manufacturing complexity. The numerical and experimental results are consistent showing the return loss of this antenna to be less than -20 dB and the axial ratio at the boresight direction to be less than 0.7 dB in the frequency range from 23.5 GHz to 24.5 GHz. In addition, the gain of this antenna is higher than 20 dB. The newly designed circularly polarized horn antenna has a simple structure and outperforms many existing circular polarization devices in high-power operations.

Characterization of expressed sequence tags from turkey skeletal muscle.

This study was designed to identify important muscle gene homologues in the turkey. Three skeletal muscle cDNA libraries representing distinct muscle developmental stages were constructed. A total of 20,042 clones were sequenced resulting in 13,023 finished high-quality sequences (trimmed, quality scored and masked) for analysis. Sequence clustering produced 1113 contigs and 4144 singletons (5257 putative transcripts). Sequences were compared by blastn to the chicken whole-genome sequence and to the Ensembl and NCBI databases to identify homologous sequences. These surveys indicated that most of the important muscle genes are included in the sequence collection. Examination of contigs identified 1288 single nucleotide polymorphisms and in 320 of those the minor allele was observed to be present in more than one sequence. This resource provides sequence variants for numerous genes in the turkey, as demonstrated by the SNP haplotypes that were constructed for 10 genes. Sequences obtained in this study provide the basis for constructing a skeletal muscle-focused microarray, a tool that will facilitate the analysis of genes expressed during turkey muscle development, as well as the expression of genes underlying the genetic basis of muscle characteristics associated with meat quality.

The effect of heat stress on thyroid hormone response and meat quality in turkeys of two genetic lines.

The current study evaluated the effect of heat stress on thyroid hormone (T(3) and T(4)) response and meat quality traits in two turkey lines: a growth-selected commercial line and a genetically unimproved control line. Birds were subjected to heat stress for different durations before harvest. Commercial line had higher pH(15min), and lightness values, but lower cook loss and marinade uptake than control line during the heat stress. There was no difference in drip loss between the two lines. The T(3) concentration was positively correlated with cook loss and was negatively correlated with marinade uptake. The thyroid hormone response during heat stress was less stable in the commercial line than in the control line and the unstable thyroid hormone response in commercial turkeys caused by heat exposure might influence the consistency of meat quality. Results of this study may provide an application in selecting turkeys which yield consistent meat quality.

Characterization of a cardiac complementary deoxyribonucleic acid library from the Turkey (Meleagris gallopavo).

Although the domestic turkey (Meleagris gallopavo) is a valuable agricultural commodity, genetic studies on this species lag behind those of other agricultural species. In this study, we examined expressed sequence tags (EST) from a turkey cardiac cDNA library constructed from 4 birds representing 2 developmental stages. A collection of 3,937 EST sequences were sequenced and analyzed for gene annotation and sequence variation. Clustering of sequences resulted in 353 contigs and 874 singletons (1,227 putative transcripts). All EST sequences were compared by BLASTN to the chicken whole genome sequence and to Ensembl and National Center for Biotechnology Information databases. The majority of significant matches correspond to genes found in the chicken. Sequence polymorphisms were identified in 310 contigs, 64 where the minor allele was observed to be present in more than 1 sequence. This study gives species-specific insight into the cardiac transcriptome of turkeys and provides resources for future studies of cardiac function.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation.

Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.

Phosphoinositide-3-kinase-dependent, MyD88-independent induction of CC-type chemokines characterizes the macrophage response to Toxoplasma gondii strains with high virulence.

Chemokines play an important role in inflammation and infection due to their ability to recruit cells of innate and adaptive immunity. Here we examined mouse macrophage chemokine responses during intracellular infections with high- and low-virulence Toxoplasma gondii strains. The high-virulence type I strain RH induced a large panel of CC-type chemokines, whereas responses elicited by strains PTG (type II) and M7741 (type III) were much weaker. Strikingly, the T. gondii-induced chemokine response occurred independently of signaling through the Toll-like receptor adaptor MyD88. Instead, production of chemokines during infection was heavily dependent upon phosphoinositide-3-kinase signaling pathways. Because infection with type I strains such as RH results in an uncontrolled proinflammatory cytokine response, we hypothesize that this virulence phenotype is a consequence of early strong induction of chemokines by type I, but not type II or III, Toxoplasma strains.