Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.

BACKGROUND: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. OBJECTIVE: We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. METHODS: In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated. RESULTS: High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541. CONCLUSION AND CLINICAL RELEVANCE: IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.

Campylobacter and Salmonella are prevalent in broiler farms in Kyushu, Japan: results of a 2-year distribution and circulation dynamics audit.

AIM: To elucidate the distribution and circulation dynamics of Campylobacter and Salmonella in Japanese chicken broiler flocks. METHODS AND RESULTS: A 2-year investigation of the distribution of Campylobacter and Salmonella was conducted in 25 broiler flocks at nine farms in Japan from 2013 to 2014. Campylobacter and Salmonella tested positive in 11 (44·0%) and 24 (96·0%) broiler flocks respectively. One hundred and ninety-five Campylobacter and 184 Salmonella isolates were characterized into 12 Campylobacter (including two novel genotypes) and three Salmonella MLST genotypes. Only Salmonella isolation between caecal and environmental samples were significantly correlated. Further, one litter sample tested positive for Salmonella before new chicks were introduced. The Campylobacter strains rapidly lost culturability within 2-18 days; in contrast, the Salmonella strains survived from 64-211 days in artificially inoculated water samples. CONCLUSION: No persistent circulation-mediated Campylobacter contamination was observed. In contrast, circulation of Salmonella in broiler houses was seen, apparently due to the litter excreted from broiler flocks, as well as Salmonella-contaminated water and feed. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provides the distribution, genotypic data and circulation dynamics of Campylobacter and Salmonella as recently observed in Japanese chicken broiler farms.

Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly.

OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively. The weights of body, brain and uterus and the contents of protein and myelin galactolipids including galactosylceramide and sulfatide were measured. RESULTS: Memory impairment and depression-like behaviors in OVX rats were recovered to the levels of sham-operated rats by RJ administration. Increased body weight and decreased uterine weight in OVX rats were recovered to the levels of sham-operated rats by 17ß-estradiol (E2) administration but not by RJ administration. In contrast, brain weight was slightly increased by RJ administration but not by E2 administration. The contents of protein and myelin galactolipids were higher in the brains of RJ-administered OVX rats than in the brains of E2-administered OVX rats. CONCLUSION: The results suggest that RJ has a beneficial effect on neurological symptoms of a menopausal disorder.

Molecular identification of the trematode Paragonimus in faecal samples from the wild cat Prionailurus bengalensis in the Da Krong Nature Reserve, Vietnam.

Conventional identification of Paragonimus species and their natural definitive hosts is based on the morphological features of adult parasites isolated from the lungs of wild mammalian hosts. However, wild animals are protected by strict regulations and sampling is not always possible. Recently, molecular techniques have been developed to identify the internal transcribed spacer (ITS) sequences of Paragonimus eggs in faeces/sputum of human patients. Also, mammalian hosts can be identified using the D-loop sequence of mitochondrial DNA in faecal samples. In this study, we used molecular techniques on faeces from wild animals collected in Da Krong Nature Reserve, Quang Tri province, central Vietnam, where Paragonimus metacercariae are highly prevalent in mountain crabs, to identify Paragonimus species and their natural definitive hosts. The results indicated that wild cats, Prionailurus bengalensis, were infected with at least three different Paragonimus species, P. westermani, P. skrjabini and P. heterotremus. Because all of these species can infect humans in Asian countries, human paragonimiasis should be considered in this area.

Metacercarial polymorphism and genetic variation of Paragonimus heterotremus (Digenea: Paragonimidae), and a re-appraisal of the taxonomic status of Paragonimus pseudoheterotremus.

Paragonimus heterotremus, which is an important pathogen for human paragonimiasis in Asia, is recognized as having the smallest metacercariae (maximum diameter < 300 µm) of any previously reported Paragonimus species. Recently, P. pseudoheterotremus has been described from Thailand as a new species having metacercariae (about 200 µm) slightly smaller than those of Thai P. heterotremus. In fact, the small size of P. pseudoheterotremus metacercariae is compatible with those of P. heterotremus from India and China. In this study in Vietnam, we found variably sized small metacercariae which are expected to consist of both P. heterotremus and P. pseudoheterotremus. Contrary to expectation, the adult flukes obtained by separate infection of experimental cats with different sized metacercariae were all identified as P. heterotremus, using both morphological and molecular characteristics. The molecular analyses of an extensive collection of P. heterotremus/P. pseudoheterotremus isolates from Asian countries also indicated that genetic distances between different populations of P. heterotremus are even larger than that between P. pseudoheterotremus and P. heterotremus. The haplotype network showed that all P. heterotremus and P. pseudoheterotremus isolates formed a P. heterotremus complex consisting of three groups with strong geographical origins. In addition, the Indian P. heterotremus group is the root of the other P. heterotremus and P. pseudoheterotremus populations. Based on the observed metacercarial polymorphisms and genetic variation in P. heterotremus, P. pseudoheterotremus should be considered a geographically isolated population of the P. heterotremus complex.

Effect of heat-killed Lactobacillus brevis SBC8803 on cutaneous arterial sympathetic nerve activity, cutaneous blood flow and transepidermal water loss in rats.

AIM: To evaluate the efficacy of the effects of heat-killed Lactobacillus brevis SBC8803 (HK-SBC8803) on the standard physiological markers of skin health of cutaneous arterial sympathetic nerve activity (CASNA), cutaneous blood flow and transepidermal water loss (TEWL) and to determine whether SBC8803 targets serotonin 5-HT3 receptors in rats. METHODS AND RESULTS: A set of three experiments were conducted to examine the effects of SBC8803 on CASNA, cutaneous blood flow and TEWL using Wistar and hairless rats. Two additional experiments further attempted to determine whether HK-SBC8803 was targeting the serotonin 5-HT3 receptors by pretreatment with the 5-HT3 antagonist granisetron. Administration of HK-SBC8803 in the first three experiments caused marked inhibition of CASNA and significant elevation of cutaneous blood flow under urethane anaesthesia as well as significant decrease in TEWL on the dorsal skin of conscious hairless rats. Pretreatment with granisetron decreased the effects of HK-SBC8803 on CASNA and cutaneous blood flow. CONCLUSIONS: These findings suggest that HK-SBC8803 reduces CASNA, increases cutaneous blood flow and decreases TEWL and that 5-HT3 receptors may be involved in CASNA and cutaneous blood flow responses. SIGNIFICANCE AND IMPACT OF THE STUDY: HK-SBC8803 could be a useful substance in the treatment/prevention of skin problems, specifically chapped or dry skin.

Evidence for B- → τ- ν(τ) with a hadronic tagging method using the full data sample of Belle.

We measure the branching fraction of B- → τ- ν(τ) using the full Υ(4S) data sample containing 772×10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events with BB pairs are tagged by reconstructing one of the B mesons decaying into hadronic final states, and B- → τ- ν(τ) candidates are detected in the recoil. We find evidence for B- → τ- ν(τ) with a significance of 3.0 standard deviations including systematic errors and measure a branching fraction B(B- → τ- ν(τ))=[0.72(-0.25)(+0.27)(stat)±0.11(syst)]×10(-4).

Genetically variant populations of Paragonimus proliferus Hsia & Chen, 1964 from central Vietnam.

Among about 50 nominal Paragonimus species, Paragonimus proliferus is rather a rare species, found only in Yunnan province, China, until our recent discovery of this species in Lai Chau province, northern Vietnam close to Yunnan, China. Here we add Quang Binh province, central Vietnam as a new endemic area of P. proliferus. Large excysted metacercariae found in mountainous crabs, Potamiscus tannanti, were morphologically identified as P. proliferus, which was confirmed further by molecular analyses. Second internal transcribed spacer (ITS2) sequences of the P. proliferus population in Quang Binh province were completely (100%) identical with those of P. proliferus populations in Lai Chau province, northern Vietnam and Yunnan province, China. However, cytochrome oxidase subunit 1 (CO1) gene sequences of Quang Binh population were significantly different (5.6%) from that of previously reported northern Vietnam and Yunnan, China populations. A phylogenetic tree revealed that all CO1 sequences of P. proliferus Quang Binh population formed a distinct group, which was clustered with northern Vietnam and Yunnan, China populations with the bootstrap value of 75%. This is the first record of the genetically variant population of P. proliferus, distribution of which is geographically remote from the previously reported endemic areas in the border between northern Vietnam and Yunnan, China, suggesting that P. proliferus may be much more widely distributed in the Indochina peninsula (or South-East Asia) than expected.

Discovery of Paragonimus skrjabini in Vietnam and its phylogenetic status in the Paragonimus skrjabini complex.

Two members of the Paragonimus skrjabini complex, P. skrjabini and P. miyazakii, are now considered as two sub-species, P. skrjabini skrjabini and P. skrjabini miyazakii. They are well known as important pathogens for human paragonimiasis in China and Japan. Recently, members of this species complex have been reported from India. Here we report the first discovery of P. skrjabini from freshwater crab hosts in Thanh Hoa province, Vietnam. For morphological and molecular phylogenetic studies, adult worms were obtained by experimental infection in cats and dogs. Molecular analyses of metacercariae and adults revealed that the P. skrjabini population from Thanh Hoa, Vietnam was almost completely identical with that from Yunnan province, China. Those populations from Thanh Hoa, Vietnam and Yunnan, China and those from Manipur, India were significantly different from P. skrjabini populations reported from other localities of China in cytochrome oxidase subunit 1 (CO1) gene sequences, indicating considerable genetic variation within the P. skrjabini complex. Moreover, low bootstrap values in the CO1 tree suggested that more variant genotypes belonging to P. skrjabini complex may be found in other Asian countries in between Vietnam and India, such as Myanmar, Laos and Thailand. Since P. skrjabini is known as a pathogen for humans, paragonimiasis cases caused by P. skrjabini might be found in Vietnam and other Asian countries.

Search for CP violation in D± meson decays to ϕπ±.

We search for CP violation in Cabibbo-suppressed charged D meson decays by measuring the difference between the CP-violating asymmetries for the Cabibbo-suppressed decays D(±)→K(+)K(-)π(±) and the Cabibbo-favored decays D(s)(±)→K(+)K(-)π(±) in the K(+)K(-) mass region of the ϕ resonance. Using 955 fb(-1) of data collected with the Belle detector, we obtain A(CP)(D+→ϕπ+)=(+0.51±0.28±0.05)%. The measurement improves the sensitivity of previous searches by more than a factor of 5. We find no evidence for direct CP violation.

Evidence for the η(b)(2S) and observation of h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ.

We report the first evidence for the η(b)(2S) using the h(b)(2P)→η(b)(2S)γ transition and the first observation of the h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ transitions. The mass and width of the η(b)(1S) and η(b)(2S) are measured to be m(η(b)(1S))=(9402.4±1.5±1.8) MeV/c(2), m(η(b)(2S))=(9999.0±3.5(-1.9)(+2.8)) MeV/c(2), and Γ(η(b)(1S))=(10.8(-3.7-2.0)(+4.0+4.5)) MeV. We also update the h(b)(1P) and h(b)(2P) mass measurements. We use a 133.4 fb(-1) data sample collected at energies near the Υ(5S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider.

Observation of new resonant structures in γγ → ωϕ, ϕϕ, and ωω.

The processes γγ → ωϕ, ϕϕ, and ωω are measured using an 870 fb(-1) data sample collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Production of vector meson pairs is clearly observed and their cross sections are measured for masses that range from threshold to 4.0 GeV. In addition to signals from well established spin-zero and spin-two charmonium states, there are resonant structures below charmonium threshold, which have not been previously observed. We report a spin-parity analysis for the new structures and determine the products of the η(c), χ(c0), and χ(c2) two-photon decay widths and branching fractions to ωϕ, ϕϕ, and ωω.

Evidence for CP violation in the decay D+ → K(S)(0)π+.

We observe evidence for CP violation in the decay D+ → K(S)(0)π+ using a data sample with an integrated luminosity of 977 fb(-1) collected by the Belle detector at the KEKB e+ e- asymmetric-energy collider. The CP asymmetry in the decay is measured to be (-0.363±0.094±0.067)%, which is 3.2 standard deviations away from zero, and is consistent with the expected CP violation due to the neutral kaon in the final state.

Precise measurement of the CP violation parameter sin2φ1 in B0→(cc¯)K0 decays.

We present a precise measurement of the CP violation parameter sin2φ1 and the direct CP violation parameter A(f) using the final data sample of 772×10(6) BB[over ¯] pairs collected at the Υ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is reconstructed in a J/ψK(S)(0), ψ(2S)K(S)(0), χ(c1)K(S)(0), or J/ψK(L)(0) CP eigenstate and its flavor is identified from the decay products of the accompanying B meson. From the distribution of proper-time intervals between the two B decays, we obtain the following CP violation parameters: sin2φ1=0.667±0.023(stat)±0.012(syst) and A(f)=0.006±0.016(stat)±0.012(syst).

Measurement of the CP-violation parameter sin2φ1 with a new tagging method at the Υ(5S) resonance.

We report a measurement of the CP-violation parameter sin2φ1 at the Υ(5S) resonance using a new tagging method, called "B-π tagging." In Υ(5S) decays containing a neutral B meson, a charged B, and a charged pion, the neutral B is reconstructed in the J/ψK(S)(0) CP-eigenstate decay channel. The initial flavor of the neutral B meson at the moment of the Υ(5S) decay is opposite to that of the charged B and may thus be inferred from the charge of the pion without reconstructing the charged B. From the asymmetry between B-π(+) and B-π(-) tagged J/ψK(S)(0) yields, we determine sin2φ1=0.57±0.58(stat)±0.06(syst). The results are based on 121 fb(-1) of data recorded by the Belle detector at the KEKB e(+)e(-) collider.

First observation of B(s)(0) → J/ψη and B(s)(0) → J/ψη'.

We report first observations of B(s)(0) → J/ψη and B(s)(0) → J/ψη'. The results are obtained from 121.4 fb(-1) of data collected at the Υ(5S) resonance with the Belle detector at the KEKB e+ e- collider. We obtain the branching fractions B(B(s)(0) → J/ψη)=[5.10±0.50(stat)±0.25(syst)(-0.79)(+1.14)(N(B(s)(*) B(s)(*))]×10(-4), and B(B(s)(0) → J/ψη')=[3.71±0.61(stat)±0.18(syst)(-0.57)(+0.83)(N(B(s)(*) B(s)(*))]×10(-4). The ratio of the two branching fractions is measured to be (B(B(s) → J/ψη'))/(B(B(s) → J/ψη))=0.73±0.14(stat)±0.02(syst).

Search for CP violation in the decays D(0)→K(S)(0)P(0).

We have searched for CP violation in the decays D(0)→K(S)(0)P(0) where P(0) denotes a neutral pseudoscalar meson that is either a π(0), η, or η' using KEKB asymmetric-energy e(+)e(-) collision data corresponding to an integrated luminosity of 791 fb(-1) collected with the Belle detector. No evidence of significant CP violation is observed. We report the most precise CP asymmetry measurement in the decay D(0)→K(S)(0)π(0) to date: A(CP)(D(0)→K(S)(0)π(0))=(-0.28±0.19±0.10)%. We also report the first measurements of CP asymmetries in the decays D(0)→K(S)(0)η and D(0)→K(S)(0)η': A(CP)(D(0)→K(S)(0)η)=(+0.54±0.51±0.16)% and A(CP)(D(0)→K(S)(0)η')=(+0.98±0.67±0.14)%, respectively.

Evidence for the suppressed decay B(-)→DK(-), D→K(+)π(-).

The suppressed decay chain B(-)→DK(-), D→K(+)π(-), where D indicates a D(¯)(0) or D(0) state, provides important information on the CP-violating angle ϕ(3). We measure the ratio R(DK) of the decay rates to the favored mode B(-)→DK(-), D→K(-)π(+) to be R(DK)=[1.63(-0.41)(+0.44)(stat)(-0.13)(+0.07)(syst)]×10(-2), which indicates the first evidence of the signal with a significance of 4.1σ. We also measure the asymmetry A(DK) between the charge-conjugate decays to be A(DK)=-0.39(-0.28)(+0.26)(stat)(-0.03)(+0.04)(syst). The results are based on the full 772×10(6) BB(¯) pair data sample collected at the Υ(4S) resonance with the Belle detector.

Observation of transverse polarization asymmetries of charged pion pairs in e+e- annihilation near √s = 10.58 GeV.

The interference fragmentation function translates the fragmentation of a quark with a transverse projection of the spin into an azimuthal asymmetry of two final-state hadrons. In e(+)e(-) annihilation the product of two interference fragmentation functions is measured. We report nonzero asymmetries for pairs of charge-ordered π(+)π(-) pairs, which indicate a significant interference fragmentation function in this channel. The results are obtained from a 672 fb(-1) data sample that contains 711 × 10(6) π(+)π(-) pairs and was collected at and near the Υ(4S) resonance, with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider.

Search for CP violation in τ±â†’K(S)0π±ντ decays at Belle.

We report on a search for CP violation in τ(±)→K(S)(0)π(±)ν(τ) decays using a data sample of 699 fb(-1) collected by the Belle experiment at the KEKB electron-positron asymmetric-energy collider. The CP asymmetry is measured in four bins of the invariant mass of the K(S)(0)π(±) system and found to be compatible with zero with a precision of O(10(-3)) in each mass bin. Limits for the CP violation parameter Im(η(S)) are given at the 90% confidence level. These limits are |Im(η(S))| < 0.026 or better, depending on the parametrization used to describe the hadronic form factors, and improve upon previous limits by 1 order of magnitude.